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Mechanotransduction of liver sinusoidal endothelial cells under varied mechanical stimuli

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Abstract

Liver sinusoidal endothelial cells (LSECs) are the gatekeeper of liver to maintain hepatic homeostasis. They are formed into the highly specialized endothelium between vascular lumen and the space of Disse and are mechanosensitive to respond varied microenvironments. Shear stress and mechanical stretch induced by blood perfusion and substrate stiffness enhancement derived from deposition of extracellular matrix (ECM) are major mechanical stimuli that surround LSECs. This review introduces how LSECs respond to the external forces in both physiological and pathological cases and what is the interplay of LSECs with other hepatic cells. Molecular mechanisms that potentiate LSECs mechanotransduction are also discussed.

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Change history

  • 19 March 2021

    The original version is updated due to equation 1 has been incorrectly appeared in PDF

Abbreviations

AFM:

Atomic force microscopy

ARFI:

Acoustic radiation force impulse imaging

BMP:

Bone morphogenic protein

BMSC:

Bone marrow stromal cell

CFD:

Computational fluid dynamics

CH:

Congestive hepatopathy

CT:

Computed tomography

Dnmt3b:

DNA methyltransferase 3b

ECM:

Extracellular matrix

eNOS:

Endothelial nitric oxide synthase

EVG:

Elastica van Gieson

F-actin:

Filamentous actin

HCV:

Hepatitis C virus

HGF:

Hepatocyte growth factor

Hh:

Hedgehog

HLH:

Helix–loop–helix

HSC:

Hepatic stellate cell

HUVEC:

Human umbilical vein endothelial cell

IAA:

Iodoacetic acid

Id1:

Inhibitor of DNA binding 1

Ihh:

Indian hedgehog

I/R:

Ischemia-reperfusion

KLF2:

Kruppel-like factor 2

LOX:

Lysyl oxidase

LPA:

Lysophosphatidic acid

LSEC:

Liver sinusoidal endothelial cell

LXRα:

Liver X receptor α

MEC:

Mammary epithelial cell

MMP9:

Matrix metalloproteinase-9

MRE:

Magnetic resonance elastography

MSC:

Mesenchymal stem cell

NAFLD:

Nonalcoholic fatty liver disease

NECD:

Notch extracellular domain

NETs:

Neutrophil extracellular traps

NICD:

Notch intracellular domain

NO:

Nitric oxide

NRP1:

Neuropilin-1

PH:

Partial hepatectomy

pIVCL:

Partial inferior vena cava ligation

PVE:

Portal vein embolization

ROS:

Reactive oxygen species

RPM:

Revolutions per minute

Shh:

Sonic hedgehog

SMC:

Smooth muscle cell

TG:

Transglutaminase

TM:

Thrombomodulin

UTE:

Ultrasound-based technique of transient elastography

VEGFR2:

Vascular endothelial cell growth factor receptor 2

VEGFR3:

Vascular endothelial cell growth factor receptor 3

YAP:

Yes-associated protein

References

  1. Poisson, J., Lemoinne, S., Boulanger, C., et al.: Liver sinusoidal endothelial cells: Physiology and role in liver diseases. J. Hepatol. 66(1), 212–227 (2017)

    Article  Google Scholar 

  2. Maslak, E., Gregorius, A., Chlopicki, S.: Liver sinusoidal endothelial cells (LSECs) function and NAFLD; NO-based therapy targeted to the liver. Pharmacol. Rep. 67(4), 689–694 (2015)

    Article  Google Scholar 

  3. DeLeve, L.D.: Vascular liver disease and the liver sinusoidal endothelial cell. In: DeLeve, L.D., Garcia-Tsao, G. (eds.) Vascular Liver Disease: Mechanisms and Management. Springer, New York (2011)

    Chapter  Google Scholar 

  4. Wisse, E.: An electron microscopic study of fenestrated endothelial lining of rat liver sinusoids. J. Ultrastruct. Res. 31(1), 125–150 (1970)

    Article  Google Scholar 

  5. Braet, F., Wisse, E.: Structural and functional aspects of liver sinusoidal endothelial cell fenestrae: a review. Comp. Hepatol. 1(1), 1 (2002)

    Article  Google Scholar 

  6. Li, P.W., Zhou, J., Li, W., et al.: Characterizing liver sinusoidal endothelial cell fenestrae on soft substrates upon AFM imaging and deep learning. Biochim. Biophys. Acta Gen. Subj. 1864(12), 129702 (2020).

    Article  Google Scholar 

  7. Wisse, E., De Zanger, R.B., Charels, K., et al.: The liver sieve—considerations concerning the structure and function of endothelial fenestrae, the sinusoidal wall and the space of Disse. Hepatology 5(4), 683–692 (1985)

    Article  Google Scholar 

  8. Shetty, S., Lalor, P.F., Adams, D.H.: Liver sinusoidal endothelial cells—gatekeepers of hepatic immunity. Nat. Rev. Gastroenterol. Hepatol. 15(9), 555–567 (2018)

    Article  Google Scholar 

  9. Marrone, G., Shah, V.H., Gracia-Sancho, J.: Sinusoidal communication in liver fibrosis and regeneration. J. Hepatol. 65(3), 608–617 (2016)

    Article  Google Scholar 

  10. Hammoutene, A., Rautou, P.: Role of liver sinusoidal endothelial cells in non-alcoholic fatty liver disease. J.. Hepatol. 70(6), 1278–1291 (2019)

    Article  Google Scholar 

  11. Vollmar, B., Menger, M.D.: The hepatic microcirculation: mechanistic contributions and therapeutic targets in liver injury and repair. Physiol. Rev. 89(4), 1269–1339 (2009)

    Article  Google Scholar 

  12. Schaffner, F., Popper, H.: Capillarization of hepatic sinusoids in man. Gastroenterology. 44(3), 239–242 (1963)

    Article  Google Scholar 

  13. Urashima, S., Tsutsumi, M., Nakase, K., et al.: Studies on capillarization of the hepatic sinusoids in alcoholic liver-disease. Alcohol Alcohol Suppl. 28(1B), 77–84 (1993)

    Article  Google Scholar 

  14. Xu, B., Broome, U., Uzunel, M., et al.: Capillarization of hepatic sinusoid by liver endothelial cell-reactive autoantibodies in patients with cirrhosis and chronic hepatitis. Am. J. Pathol. 163(4), 1275–1289 (2003)

    Article  Google Scholar 

  15. DeLeve, L.D.: Liver sinusoidal endothelial cells in hepatic fibrosis. Hepatology. 61(5), 1740–1746 (2015)

    Article  Google Scholar 

  16. You, Z.F., Zhou, L., Li, W.J., et al.: Mechanical microenvironment as a key cellular regulator in the liver. Acta Mech. Sin. 35(2), 289–298 (2019)

    Article  Google Scholar 

  17. Eipel, C., Abshagen, K., Vollmar, B.: Regulation of hepatic blood flow: the hepatic arterial buffer response revisited. World J. Gastroenterol. 16(48), 6046–6057 (2010)

    Article  Google Scholar 

  18. Grande Nakazato, P.C., Victorino, J.P., Fina, C.F., et al.: Liver ischemia and reperfusion injury. Pathophysiology and new horizons in preconditioning and therapy. Acta Cir. Bras. 33(8), 723–735 (2018)

    Article  Google Scholar 

  19. Golse, N., Bucur, P.O., Adam, R., et al.: New paradigms in post-hepatectomy liver failure. J. Gastrointest. Surg. 17(3), 593–605 (2013)

    Article  Google Scholar 

  20. Lorenz, L., Axnick, J., Buschmann, T., et al.: Mechanosensing by beta 1 integrin induces angiocrine signals for liver growth and survival. Nature 562(7725), 128–132 (2018)

    Article  Google Scholar 

  21. DeLeve, L.D., Wang, X.D., Guo, Y.M.: Sinusoidal endothelial cells prevent rat stellate cell activation and promote reversion to quiescence. Hepatology 48(3), 920–930 (2008)

    Article  Google Scholar 

  22. Garcia-Pagan, J.C., Gracia-Sancho, J., Bosch, J.: Functional aspects on the pathophysiology of portal hypertension in cirrhosis. J. Hepatol. 57(2), 458–461 (2012)

    Article  Google Scholar 

  23. Thabut, D., Shah, V.: Intrahepatic angiogenesis and sinusoidal remodeling in chronic liver disease: new targets for the treatment of portal hypertension? J. Hepatol. 53(5), 976–980 (2010)

    Article  Google Scholar 

  24. Georges, P.C., Hui, J.J., Gombos, Z., et al.: Increased stiffness of the rat liver precedes matrix deposition: implications for fibrosis. Am. J. Physiol. Gastrointest. Liver Physiol. 293(6), G1147–G1154 (2007)

    Article  Google Scholar 

  25. Ajmera, V.H., Liu, A., Singh, S., et al.: Clinical utility of an increase in magnetic resonance elastography in predicting fibrosis progression in nonalcoholic fatty liver disease. Hepatology 71(3), 849–860 (2020)

    Article  Google Scholar 

  26. Xing, X., Yan, Y.L., Shen, Y., et al.: Liver fibrosis with two-dimensional shear-wave elastography in patients with autoimmune hepatitis. Expert Rev. Gastroenterol. Hepatol. 14(7), 631–638 (2020)

    Article  Google Scholar 

  27. Higuchi, M., Tamaki, N., Kurosaki, M., et al: Changes of liver stiffness measured by magnetic resonance elastography during direct-acting antivirals treatment in patients with chronic hepatitis C. J. Med. Virol. Online ahead of print

  28. Medrano, L.M., Garcia-Broncano, P., Berenguer, J., et al.: Elevated liver stiffness is linked to increased biomarkers of inflammation and immune activation in HIV/hepatitis C virus-coinfected patients. AIDS 32(9), 1095–1105 (2018)

    Article  Google Scholar 

  29. Ko, B.J., Kim, Y.S., Kim, S.G., et al.: Relationship between 25-hydroxyvitamin d levels and liver fibrosis as assessed by transient elastography in patients with chronic liver disease. Gut Liver. 10(5), 818–825 (2016)

    Article  Google Scholar 

  30. Davies, P.F.: Flow-mediated endothelial mechanotransduction. Physiol. Rev. 75(3), 519–560 (1995)

    Article  Google Scholar 

  31. Ballermann, B.J., Dardik, A., Eng, E., et al.: Shear stress and the endothelium. Kidney Int. 54, S100–S108 (1998)

    Article  Google Scholar 

  32. Johnson, F.P.: The development of the lobule of the pig’s liver. Am. J. Anat. 25(3), 299–331 (1919)

    Article  Google Scholar 

  33. Deal, C.P., Green, H.D.: Comparison of changes in mesenteric resistance following splanchnic nerve stimulation with responses to epinephrine and norepinephrine. Circ. Res. 4(1), 38–44 (1956)

    Article  Google Scholar 

  34. Wen, B., Liang, J., Deng, X., et al.: Effect of fluid shear stress on portal vein remodeling in a rat model of portal hypertension. Gastroenterol. Res. Pract. 41, 1–7 (2015)

    Article  Google Scholar 

  35. Aghasafari, P., Pidaparti, R.: Influence of tidal-volume setting, emphysema and ARDS on human alveolar sacs mechanics. Acta Mech. Sin. 34(5), 983–993 (2018)

    Article  Google Scholar 

  36. Liu, Z.M., Zhao, S.W., Li, Y.J., et al.: Influence of coronary bifurcation angle on atherosclerosis. Acta Mech. Sin. 35(6), 1269–1278 (2019)

    Article  Google Scholar 

  37. Debbaut, C., Vierendeels, J., Casteleyn, C., et al.: Perfusion characteristics of the human hepatic microcirculation based on three-dimensional reconstructions and computational fluid dynamic analysis. J. Biomech. Eng. 134(1), 011003 (2012)

    Article  Google Scholar 

  38. Wei, W., Pu, Y.S., Wang, X.K., et al.: Wall shear stress in portal vein of cirrhotic patients with portal hypertension. World J. Gastroenterol. 23(18), 3279–3286 (2017)

    Article  Google Scholar 

  39. Peeters, G., Debbaut, C., Cornillie, P., et al.: A multilevel modeling framework to study hepatic perfusion characteristics in case of liver cirrhosis. J. Biomech. Eng. 137(5), 051007 (2015)

    Article  Google Scholar 

  40. Hu, J.R., Lu, S.Q., Feng, S.L., et al.: Flow dynamics analyses of pathophysiological liver lobules using porous media theory. Acta Mech. Sin. 33(4), 823–832 (2017)

    Article  Google Scholar 

  41. Fernandez, M.: Molecular pathophysiology of portal hypertension. Hepatology 61(4), 1406–1415 (2015)

    Article  Google Scholar 

  42. Shah, V., Haddad, F.G., Garcia-Cardena, G., et al.: Liver sinusoidal endothelial cells are responsible for nitric oxide modulation of resistance in the hepatic sinusoids. J. Clin. Invest. 100(11), 2923–2930 (1997)

    Article  Google Scholar 

  43. Gracia-Sancho, J., Russo, L., Garcia-Caldero, H., et al.: Endothelial expression of transcription factor Kruppel-like factor 2 and its vasoprotective target genes in the normal and cirrhotic rat liver. Gut 60(4), 517–524 (2011)

    Article  Google Scholar 

  44. Conway, E.M.: Thrombomodulin and its role in inflammation. Semin. Immunopathol. 34(1), 107–125 (2012)

    Article  Google Scholar 

  45. Marrone, G., Russo, L., Rosado, E., et al.: The transcription factor KLF2 mediates hepatic endothelial protection and paracrine endothelial-stellate cell deactivation induced by statins. J. Hepatol. 58(1), 98–103 (2013)

    Article  Google Scholar 

  46. Garcea, G., Maddern, G.J.: Liver failure after major hepatic resection. J. Hepato-Biliary Pancreatic Surg. 16(2), 145–155 (2009)

    Article  Google Scholar 

  47. Schoen, J.M., Wang, H.H., Minuk, G.Y., et al.: Shear stress-induced nitric oxide release triggers the liver regeneration cascade. Nitric Oxide 5(5), 453–464 (2001)

    Article  Google Scholar 

  48. Braet, F., Shleper, M., Paizi, M., et al.: Liver sinusoidal endothelial cell modulation upon resection and shear stress in vitro. Comp. Hepatol. 3(1), 7 (2004)

    Article  Google Scholar 

  49. Kim, H.J., Chung, H., Yoo, Y.G., et al.: Inhibitor of DNA binding 1 activates vascular endothelial growth factor through enhancing the stability and activity of hypoxia-inducible factor-1 alpha. Mol. Cancer Res. 5(4), 321–329 (2007)

    Article  Google Scholar 

  50. Wang, H., Yu, Y., Guo, R.W., et al.: Inhibitor of DNA binding-1 promotes the migration and proliferation of endothelial progenitor cells in vitro. Mol. Cell. Biochem. 335(1–2), 19–27 (2010)

    Article  Google Scholar 

  51. Ding, B.S., Nolan, D.J., Butler, J.M., et al.: Inductive angiocrine signals from sinusoidal endothelium are required for liver regeneration. Nature 468(7321), 310–315 (2010)

    Article  Google Scholar 

  52. Yamanaka, K., Hatano, E., Narita, M., et al.: Olprinone attenuates excessive shear stress through up-regulation of endothelial nitric oxide synthase in a rat excessive hepatectomy model. Liver Transplant. 17(1), 60–69 (2011)

    Article  Google Scholar 

  53. Morsiani, E., Mazzoni, M., Aleotti, A., et al.: Increased sinusoidal wall permeability and liver fatty change after two-thirds hepatectomy: an ultrastructural study in the rat. Hepatology 21(2), 539–544 (1995)

    Google Scholar 

  54. Torii, T., Miyazawa, M., Koyama, I.: Effect of continuous application of shear stress on liver tissue: continuous application of appropriate shear stress has advantage in protection of liver tissue. Transpl. Proc. 37(10), 4575–4578 (2005)

    Article  Google Scholar 

  55. Asencio, J.M., Garcia-Sabrido, J.L., Lopez-Baena, J.A., et al.: Preconditioning by portal vein embolization modulates hepatic hemodynamics and improves liver function in pigs with extended hepatectomy. Surgery 161(6), 1489–1501 (2017)

    Article  Google Scholar 

  56. Asakura, T., Ohkohchi, N., Orii, T., et al.: Portal vein pressure is the key for successful liver transplantation of an extremely small graft in the pig model. Transpl. Int. 16(6), 376–382 (2003)

    Article  Google Scholar 

  57. Lentsch, A.B., Kato, A., Yoshidome, H., et al.: Inflammatory mechanisms and therapeutic strategies for warm hepatic ischemia/reperfusion injury. Hepatology 32(2), 169–173 (2000)

    Article  Google Scholar 

  58. Peralta, C., Jimenez-Castro, M.B., Gracia-Sancho, J.: Hepatic ischemia and reperfusion injury: Effects on the liver sinusoidal milieu. J. Hepatol. 59(5), 1094–1106 (2013)

    Article  Google Scholar 

  59. Huet, P.M., Nagaoka, M.R., Desbiens, G., et al.: Sinusoidal endothelial cell and hepatocyte death following cold ischemia-warm reperfusion of the rat liver. Hepatology 39(4), 1110–1119 (2004)

    Article  Google Scholar 

  60. Garcia-Valdecasas, J.C., Fondevila, C.: In-vivo normothermic recirculation: an update. Curr. Opin. Org. Transpl. 15(2), 173–176 (2010)

    Article  Google Scholar 

  61. Xue, S., He, W.Y., Zeng, X.P., et al.: Hypothermic machine perfusion attenuates ischemia/reperfusion injury against rat livers donated after cardiac death by activating the Keap1/Nrf2-ARE signaling pathway. Mol. Med. Rep. 18(1), 815–826 (2018)

    Google Scholar 

  62. Chatterjee, S., Nieman, G.F., Christie, J.D., et al.: Shear stress-related mechanosignaling with lung ischemia: lessons from basic research can inform lung transplantation. Am. J. Physiol. Lung Cell. Mol. Physiol. 307(9), L668–L680 (2014)

    Article  Google Scholar 

  63. Hammoutene, A., Biquard, L., Lasselin, J., et al.: A defect in endothelial autophagy occurs in patients with non-alcoholic steatohepatitis and promotes inflammation and fibrosis. J. Hepatol 72(3), 528–538 (2020)

    Article  Google Scholar 

  64. Boteon, Y.L., Laing, R., Mergental, H., et al.: Mechanisms of autophagy activation in endothelial cell and their targeting during normothermic machine liver perfusion. World J. Gastroenterol. 23(48), 8443–8451 (2017)

    Article  Google Scholar 

  65. Noh, J.K., Jung, J.G., Jang, E.M., et al.: Live cell-imaging perfusion culture system of liver sinusoidal endothelial cells to mimic stem cell engraftment in liver. Transpl. Proc. 44(4), 1116–1119 (2012)

    Article  Google Scholar 

  66. Shetty, S., Weston, C.J., Oo, Y.H., et al.: Common lymphatic endothelial and vascular endothelial receptor-1 mediates the transmigration of regulatory T cells across human hepatic sinusoidal endothelium. J. Immunol. 186(7), 4147–4155 (2011)

    Article  Google Scholar 

  67. Busse, R., Fleming, I.: Pulsatile stretch and shear stress: physical stimuli determining the production of endothelium-derived relaxing factors. J. Vasc. Res. 35(2), 73–84 (1998)

    Article  Google Scholar 

  68. Rabbany, S.Y., Ding, B.S., Larroche, C., et al.: Mechanosensory pathways in angiocrine mediated tissue regeneration. In: Gefen, A., Aviv, R. (eds.) Studies in Mechanobiology, Tissue Engineering and Biomaterials. Springer, Berlin, Heidelberg, New York (2013)

    Google Scholar 

  69. Hilscher, M.B., Sehrawat, T., Arab, J.P., et al.: Mechanical stretch increases expression of CXCL1 in liver sinusoidal endothelial cells to recruit neutrophils, generate sinusoidal microthombi, and promote portal hypertension. Gastroenterology. 157(1), 193–209 (2019)

    Article  Google Scholar 

  70. Wanless, I.R., Liu, J.J., Butany, J.: Role of thrombosis in the pathogenesis of congestive hepatic-fibrosis (cardiac cirrhosis). Hepatology. 21(5), 1232–1237 (1995)

    Google Scholar 

  71. Soydemir, S., Comella, O., Abdelmottaleb, D., et al.: Does mechanocrine signaling by liver sinusoidal endothelial cells offer new opportunities for the development of anti-fibrotics? Front. Med. 6, 312 (2020)

    Article  Google Scholar 

  72. Kawai, M., Naruse, K., Komatsu, S., et al.: Mechanical stress-dependent secretion of interleukin 6 by endothelial cells after portal vein embolization: clinical and experimental studies. J. Hepatol. 37(2), 240–246 (2002)

    Article  Google Scholar 

  73. Cressman, D.E., Greenbaum, L.E., DeAngelis, R.A., et al.: Liver failure and defective hepatocyte regeneration in interleukin-6-deficient mice. Science 274(5291), 1379–1383 (1996)

    Article  Google Scholar 

  74. Sakamoto, T., Liu, Z.J., Murase, N., et al.: Mitosis and apoptosis in the liver of interleukin-6-deficient mice after partial hepatectomy. Hepatology 29(2), 403–411 (1999)

    Article  Google Scholar 

  75. Bohm, F., Kohler, U.A., Speicher, T., et al.: Regulation of liver regeneration by growth factors and cytokines. EMBO Mol. Med. 2(8), 294–305 (2010)

    Article  Google Scholar 

  76. Olle, E.W., Ren, X.D., McClintock, S.D., et al.: Matrix metalloproteinase-9 is an important factor in hepatic regeneration after partial hepatectomy in mice. Hepatology 44(3), 540–549 (2006)

    Article  Google Scholar 

  77. Handorf, A.M., Zhou, Y.X., Halanski, M.A., et al.: Tissue stiffness dictates development, homeostasis, and disease progression. Organogenesis 11(1), 1–15 (2015)

    Article  Google Scholar 

  78. Sandrin, L., Fourquet, B., Hasquenoph, J.M., et al.: Transient elastography: A new noninvasive method for assessment of hepatic fibrosis. Ultrasound Med. Biol. 29(12), 1705–1713 (2003)

    Article  Google Scholar 

  79. Mueller, S., Sandrin, L.: Liver stiffness: a novel parameter for the diagnosis of liver disease. Hepat. Med. 2, 49–67 (2010)

    Google Scholar 

  80. Palmeri, M.L., Wang, M.H., Dahl, J.J., et al.: Quantifying hepatic shear modulus in vivo using acoustic radiation force. Ultrasound Med. Biol. 34(4), 546–558 (2008)

    Article  Google Scholar 

  81. Wegner, M., Iskender, E., Azzarok, A., et al.: Comparison of acoustic radiation force impulse imaging with the convex probe 6C1 and linear probe 9L4. Medicine (Baltimore). 99(16), e19701 (2020)

    Article  Google Scholar 

  82. Dahl, J.J., Pinton, G.F., Palmeri, M.L., et al.: A parallel tracking method for acoustic radiation force impulse imaging. IEEE Trans. Ultrason. Ferroelectr. Freq. Control 54(2), 301–312 (2007)

    Article  Google Scholar 

  83. Palmeri, M.L., Sharma, A.C., Bouchard, R.R., et al.: A finite-element method model of soft tissue response to impulsive acoustic radiation force. IEEE Trans. Ultrason. Ferroelectr. Freq. Control 52(10), 1699–1712 (2005)

    Article  Google Scholar 

  84. Muthupillai, R., Lomas, D.J., Rossman, P.J., et al.: Magnetic-resonance elastography by direct visualization of propagating acoustic strain waves. Science 269(5232), 1854–1857 (1995)

    Article  Google Scholar 

  85. Venkatesh, S.K., Yin, M., Ehman, R.L.: Magnetic resonance elastography of liver: technique, analysis, and clinical applications. J. Magn. Reson. Imaging 37, 544–555 (2013)

    Article  Google Scholar 

  86. Taouli, B., Ehman, R.L., Reeder, S.B.: Advanced MRI methods for assessment of chronic liver disease. AJR Am. J .Roentgenol. 193(1), 14–27 (2009)

    Article  Google Scholar 

  87. Gang, Z., Qi, Q., Jing, C., et al.: Measuring microenvironment mechanical stress of rat liver during diethylnitrosamine induced hepatocarcinogenesis by atomic force microscope. Microsc. Res. Tech. 72(9), 672–678 (2009)

    Article  Google Scholar 

  88. Hu, J.R., Huang, D.D., Zhang, Y., et al.: Global mapping of live cell mechanical features using PeakForce QNM AFM. Biophys. Rep. 6(1), 9–18 (2020)

    Article  Google Scholar 

  89. Lin, D.C., Dimitriadis, E.K., Horkay, F.: Advances in the mechanical characterization of soft materials by nanoindentation. Recent Res. Dev. Biophys. 5, 333–370 (2006)

    Google Scholar 

  90. Desai, S.S., Tung, J.C., Zhou, V.X., et al.: Physiological ranges of matrix rigidity modulate primary mouse hepatocyte function in part through hepatocyte nuclear factor 4 alpha. Hepatology 64(1), 261–275 (2016)

    Article  Google Scholar 

  91. Butt, H.J., Jaschke, M., Ducker, W.: Measuring surface forces in aqueous-electrolyte solution with the atomic-force microscope. Bioelectrochem. Bioenerget. 38(1), 191–201 (1995)

    Article  Google Scholar 

  92. Efremov, Y.M., Okajima, T., Raman, A.: Measuring viscoelasticity of soft biological samples using atomic force microscopy. Soft Matter 16(1), 64–81 (2020)

    Article  Google Scholar 

  93. Bastard, C., Bosisio, M.R., Chabert, M., et al.: Transient micro-elastography: a novel non-invasive approach to measure liver stiffness in mice. World J. Gastroenterol. 17(8), 968–975 (2011)

    Article  Google Scholar 

  94. Hoodeshenas, S., Yin, M., Venkatesh, S.K.: Magnetic resonance elastography of liver: current update. Top. Magn. Reson. Imaging 27(5), 319–333 (2018)

    Article  Google Scholar 

  95. Baiocchini, A., Montaldo, C., Conigliaro, A., et al.: Extracellular matrix molecular remodeling in human liver fibrosis evolution. PLoS ONE 11(3), e0151736 (2016)

    Article  Google Scholar 

  96. Abe, T., Hashiguchi, A., Yamazaki, K., et al.: Quantification of collagen and elastic fibers using whole-slide images of liver biopsy specimens. Patho.l Int. 63(6), 305–310 (2013)

    Article  Google Scholar 

  97. Kolacna, L., Bakesova, J., Varga, F., et al.: Biochemical and biophysical aspects of collagen nanostructure in the extracellular matrix. Physiol. Res. 56(Suppl 1), S51–S60 (2007)

    Article  Google Scholar 

  98. Barry-Hamilton, V., Spangler, R., Marshall, D., et al.: Allosteric inhibition of lysyl oxidase-like-2 impedes the development of a pathologic microenvironment. Nat. Med. 16(9), 1009–1017 (2010)

    Article  Google Scholar 

  99. Ford, A.J., Jain, G., Rajagopalan, P.: Designing a fibrotic microenvironment to investigate changes in human liver sinusoidal endothelial cell function. Acta Biomater. 24, 220–227 (2015)

    Article  Google Scholar 

  100. Juin, A., Planus, E., Guillemot, F., et al.: Extracellular matrix rigidity controls podosome induction in microvascular endothelial cells. Biol. Cell 105(1), 46–57 (2013)

    Article  Google Scholar 

  101. Liu, L.W., You, Z.F., Yu, H.S., et al.: Mechanotransduction-modulated fibrotic microniches reveal the contribution of angiogenesis in liver fibrosis. Nat. Mater. 16(12), 1252–1261 (2017)

    Article  Google Scholar 

  102. Bok, J., Zenczak, C., Hwang, C.H., et al.: Auditory ganglion source of Sonic hedgehog regulates timing of cell cycle exit and differentiation of mammalian cochlear hair cells. Proc. Natl. Acad. Sci. USA 110(34), 13869–13874 (2013)

    Article  Google Scholar 

  103. Masai, I., Yamaguchi, M., Tonou-Fujimori, N., et al.: The hedgehog-PKA pathway regulates two distinct steps of the differentiation of retinal ganglion cells: the cell-cycle exit of retinoblasts and their neuronal maturation. Development 132(7), 1539–1553 (2005)

    Article  Google Scholar 

  104. Abramyan, J.: Hedgehog signaling and embryonic craniofacial disorders. J. Dev. Biol. 7(2), 9 (2019)

    Article  Google Scholar 

  105. Binder, M., Chmielarz, P., McKinnon, P.J., et al.: Functionally distinctive Ptch receptors establish multimodal Hedgehog signaling in the tooth epithelial stem cell niche. Stem Cells 37(9), 1238–1248 (2019)

    Article  Google Scholar 

  106. Wang, C.D., Shan, S.Z., Wang, C.L., et al.: Mechanical stimulation promote the osteogenic differentiation of bone marrow stromal cells through epigenetic regulation of Sonic Hedgehog. Exp. Cell. Res. 352(2), 346–356 (2017)

    Article  Google Scholar 

  107. Wu, Q.Q., Zhang, Y., Chen, Q.: Indian hedgehog is an essential component of mechanotransduction complex to stimulate chondrocyte proliferation. J. Biol. Chem. 276(38), 35290–35296 (2001)

    Article  Google Scholar 

  108. Morrow, D., Sweeney, C., Birney, Y.A., et al.: Biomechanical regulation of hedgehog signaling in vascular smooth muscle cells in vitro and in vivo. Am. J. Physiol. Cell Physiol. 292(1), C488–C496 (2007)

    Article  Google Scholar 

  109. Hoey, D.A., Downs, M.E., Jacobs, C.R.: The mechanics of the primary cilium: an intricate structure with complex function. J. Biomech. 45(1), 17–26 (2012)

    Article  Google Scholar 

  110. Corbit, K.C., Aanstad, P., Singla, V., et al.: Vertebrate Smoothened functions at the primary cilium. Nature 437(7061), 1018–1021 (2005)

    Article  Google Scholar 

  111. Kim, J., Kato, M., Beachy, P.A.: Gli2 trafficking links Hedgehog-dependent activation of Smoothened in the primary cilium to transcriptional activation in the nucleus. Proc. Natl. Acad. Sci. USA 106(51), 21666–21671 (2009)

    Article  Google Scholar 

  112. Xie, G.H., Choi, S.S., Syn, W.K., et al.: Hedgehog signalling regulates liver sinusoidal endothelial cell capillarization. Gut 62(2), 299–309 (2013)

    Article  Google Scholar 

  113. Pereira, T.D., Witek, R.P., Syn, W.K., et al.: Viral factors induce Hedgehog pathway activation in humans with viral hepatitis, cirrhosis, and hepatocellular carcinoma. Lab. Invest. 90(12), 1690–1703 (2010)

    Article  Google Scholar 

  114. Witek, R.P., Yang, L., Liu, R.S., et al.: Liver cell-derived microparticles activate hedgehog signaling and alter gene expression in hepatic endothelial cells. Gastroenterology 136(1), 320–330 (2009)

    Article  Google Scholar 

  115. Xing, Y., Zhao, T.T., Gao, X.Y., et al.: Liver X receptor alpha is essential for the capillarization of liver sinusoidal endothelial cells in liver injury. Sci. Rep. 6, 11 (2016)

    Google Scholar 

  116. Yang, X., Wang, Z.M., Kai, J., et al.: Curcumol attenuates liver sinusoidal endothelial cell angiogenesis via regulating Glis-PROX1-HIF-1 alpha in liver fibrosis. Cell Prolif. 53(3), 134–144 (2020)

    Article  Google Scholar 

  117. Weinmaster, G., Fischer, J.A.: Notch ligand ubiquitylation: what is it good for? Dev. Cell. 21(1), 134–44 (2011)

    Article  Google Scholar 

  118. Henrique, D., Schweisguth, F.: Mechanisms of Notch signaling: a simple logic deployed in time and space. Development 146(3), dev172148 (2019).

    Article  Google Scholar 

  119. D’Souza, B., Miyamoto, A., Weinmaster, G.: The many facets of Notch ligands. Oncogene 27(38), 5148–5167 (2008)

    Article  Google Scholar 

  120. Kopan, R.: Notch Signaling. Cold Spring Harb. Perspect. Biol. 4(10), a011213 (2012). 

    Article  Google Scholar 

  121. Shen, W., Sun, J.J.: Different modes of Notch activation and strength regulation in the spermathecal secretory lineage. Development 147(3), dev184390 (2020). 

    Article  Google Scholar 

  122. Meloty-Kapella, L., Shergill, B., Kuon, J., et al.: Notch ligand endocytosis generates mechanical pulling force dependent on dynamin, epsins, and actin. Dev. Cell 22(6), 1299–1312 (2012)

    Article  Google Scholar 

  123. Mack, J.J., Mosqueiro, T.S., Archer, B.J., et al.: NOTCH1 is a mechanosensor in adult arteries. Nat. Commun. 8(1), 1620 (2017)

    Article  Google Scholar 

  124. Loomes, K.M., Taichman, D.B., Glover, C.L., et al.: Characterization of Notch receptor expression in the developing mammalian heart and liver. Am. J. Med. Genet. 112(2), 181–189 (2002)

    Article  Google Scholar 

  125. Cuervo, H., Nielsen, C.M., Simonetto, D.A., et al.: Endothelial Notch signaling is essential to prevent hepatic vascular malformations in mice. Hepatology 64(4), 1302–1316 (2016)

    Article  Google Scholar 

  126. Duan, J.-L., Ruan, B., Yan, X.-C., et al.: Endothelial Notch activation reshapes the angiocrine of sinusoidal endothelia to aggravate liver fibrosis and blunt regeneration in mice. Hepatology 68(2), 677–690 (2018)

    Article  Google Scholar 

  127. Chen, L.Y., Gu, T.Y., Li, B.H.: Delta-like ligand 4/DLL4 regulates the capillarization of liver sinusoidal endothelial cell and liver fibrogenesis. Biochim. Biophys. Acta Mol. Cell. Res. 1866(10), 1663–1675 (2019)

    Article  Google Scholar 

  128. Bai, H.B., Zhang, N.L., Xu, Y., et al.: Yes-associated protein regulates the hepatic response after bile duct ligation. Hepatology 56(3), 1097–1107 (2012)

    Article  Google Scholar 

  129. Zhang, C.X., Bian, M.L., Chen, X.R., et al.: Oroxylin A prevents angiogenesis of LSECs in liver fibrosis via inhibition of YAP/HIF-1 signaling. J. Cell. Biochem. 119(2), 2258–2268 (2018)

    Article  Google Scholar 

  130. Zheng, Y.G., Pan, D.J.: The Hippo signaling pathway in development and disease. Dev. Cell 50(3), 264–282 (2019)

    Article  Google Scholar 

  131. Dupont, S., Morsut, L., Aragona, M., et al.: Role of YAP/TAZ in mechanotransduction. Nature 474(7350), 179–183 (2011)

    Article  Google Scholar 

  132. Totaro, A., Panciera, T., Piccolo, S.: YAP/TAZ upstream signals and downstream responses. Nat. Cell. Biol. 20(8), 888–899 (2018)

    Article  Google Scholar 

  133. Nakajima, H., Yamamoto, K., Agarwala, S., et al.: Flow-dependent endothelial YAP regulation contributes to vessel maintenance. Dev. Cell 40(6), 523–536 (2017)

    Article  Google Scholar 

  134. Neto, F., Klaus-Bergmann, A., Ong, Y.T., et al.: YAP and TAZ regulate adherens junction dynamics and endothelial cell distribution during vascular development. eLife 7, e31037 (2018). 

    Article  Google Scholar 

  135. Watanabe, N., Tohyama, K., Yamashiro, S.: Mechanostress resistance involving formin homology proteins: G- and F-actin homeostasis-driven filament nucleation and helical polymerization-mediated actin polymer stabilization. Biochem. Biophys. Res. Commun. 506(2), 323–329 (2018)

    Article  Google Scholar 

  136. Wang, Y.Z., Qian, J.: Buckling of filamentous actin bundles in filopodial protrusions. Acta Mech. Sin. 35(2), 365–375 (2019)

    Article  MathSciNet  Google Scholar 

  137. Kadzik, R.S., Homa, K.E., Kovar, D.R.: F-actin cytoskeleton network self-organization through competition and cooperation. Annu. Rev. Cell. Dev. Biol. 36, 35–60 (2020)

    Article  Google Scholar 

  138. Merino, F., Pospich, S., Raunser, S.: Towards a structural understanding of the remodeling of the actin cytoskeleton. Semin. Cell. Dev. Biol. 102, 51–64 (2020)

    Article  Google Scholar 

  139. Sun, X.Y., Phua, D.Y.Z., Axiotakis, L.J., et al.: Mechanosensing through direct binding of tensed f-actin by LIM domains. Dev. Cell 55(4), 468–482 (2020)

    Article  Google Scholar 

  140. Stricker, J., Falzone, T., Gardel, M.L.: Mechanics of the F-actin cytoskeleton. J. Biomech. 43(1), 9–14 (2010)

    Article  Google Scholar 

  141. Monkemoller, V., Oie, C., Hubner, W., et al.: Multimodal super-resolution optical microscopy visualizes the close connection between membrane and the cytoskeleton in liver sinusoidal endothelial cell fenestrations. Sci. Rep. 5, 16279 (2015).

    Article  Google Scholar 

  142. Zapotoczny, B., Szafranska, K., Owczarczyk, K., et al.: Atomic force microscopy reveals the dynamic morphology of fenestrations in live liver sinusoidal endothelial cells. Sci. Rep. 7(1), 7994 (2017)

    Article  Google Scholar 

  143. Zapotoczny, B., Braet, F., Kus, E., et al.: Actin-spectrin scaffold supports open fenestrae in liver sinusoidal endothelial cells. Traffic 20(12), 932–942 (2019)

    Article  Google Scholar 

  144. Ridley, A.J., Hall, A.: The small GTP-binding protein rho regulates the assembly of focal adhesions and actin stress fibers in response to growth-factors. Cell 70(3), 389–399 (1992)

    Article  Google Scholar 

  145. Yokomori, H., Yoshimura, K., Funakoshi, S., et al.: Rho modulates hepatic sinusoidal endothelial fenestrae via regulation of the actin cytoskeleton in rat endothelial cells. Lab. Invest. 84(7), 857–864 (2004)

    Article  Google Scholar 

  146. Beijert, I., Mert, S., Huang, V., et al.: Endothelial dysfunction in steatotic human donor livers: a pilot study of the underlying mechanism during subnormothermic machine perfusion. Transpl. Direct 4(5), e345 (2018)  

    Article  Google Scholar 

  147. Du, Y., Li, N., Yang, H., et al.: Mimicking liver sinusoidal structures and functions using a 3D-configured microfluidic chip. Lab. Chip 17(5), 782–794 (2017)

    Article  Google Scholar 

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (Grants 91642203, 31627804, and 31870930), the Scientific Instrument Developing Project, Strategic Priority Research Program and Frontier Science Key Project of Chinese Academy of Sciences (Grants GJJSTU20190005, QYZDJ-SSW-JSC018 and XDB22040101).

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Authors and Affiliations

  1. Center for Biomechanics and Bioengineering, Key Laboratory of Microgravity (National Microgravity Laboratory), and Beijing Key Laboratory of Engineered Construction and Mechanobiology, Institute of Mechanics, Chinese Academy of Sciences, Beijing, 100190, China

    Xinyu Shu, Ning Li, Yi Wu, Wang Li, Xiaoyu Zhang, Peiwen Li, Dongyuan Lü, Shouqin Lü & Mian Long

  2. School of Engineering Sciences, University of Chinese Academy of Sciences, Beijing, 100049, China

    Xinyu Shu, Ning Li, Yi Wu, Wang Li, Xiaoyu Zhang, Dongyuan Lü, Shouqin Lü & Mian Long

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  1. Xinyu Shu
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Correspondence to Ning Li or Mian Long.

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Shu, X., Li, N., Wu, Y. et al. Mechanotransduction of liver sinusoidal endothelial cells under varied mechanical stimuli. Acta Mech. Sin. 37, 201–217 (2021). https://doi.org/10.1007/s10409-021-01057-3

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