Abstract
Objective
The effects of hydraulic pressure on renal tubular epithelial-myofibroblast transdifferentiation (TEMT) were investigated.
Methods
We applied hydraulic pressure (50 cmH2O) to normal rat kidney tubular epithelial cells (NRK52E) for different durations. Furthermore, different pressure magnitudes were applied to cells. The morphology, cytoskeleton, and expression of myofibroblastic marker protein and transforming growth factor-β1 (TGF-β1) of NRK52E cells were examined. Results: Disorganized actin filaments and formation of curling clusters in actin were seen in the cytoplasm of pressurized cells. We verified that de novo expression of α-smooth muscle actin induced by pressure, which indicated TEMT, was dependent on both the magnitude and duration of pressure. TGF-β1 expression was significantly upregulated under certain conditions, which implies that the induction of TEMT by hydraulic pressure is related with TGF-β1.
Conclusion
We illustrate for the first time that hydraulic pressure can induce TEMT in a pressure magnitude- and duration-dependent manner, and that this TEMT is accompanied by TGF-β1 secretion.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Cheng, M., Wu, J., Liu, X.H., Li, Y., Nie, Y.M., Li, L., Chen, H.Q., 2007. Low shear stress-induced interleukin-8 mRNA expression in endothelial cells is mechanotransduced by integrins and the cytoskeleton. Endothelium, 14(6):265–273. [doi:10.1080/10623320701678169]
Cowger, N.L., Benes, E., Allen, P.L., Hammond, T.G., 2002. Expression of renal cell protein markers is dependent on initial mechanical culture conditions. J. Appl. Physiol., 92(2):691–700.
Deen, W.M., Maddox, D.A., Robertson, C.R., Brenner, B.M., 1974. Dynamics of glomerular ultrafiltration in the rat. VII: response to reduced renal mass. Am. J. Physiol., 227(3):556–562.
Essig, M., Friedlander, G., 2003. Shear-stress-responsive signal transduction mechanisms in renal proximal tubule cells. Curr. Opin. Nephrol. Hypertens., 12(1):31–34. [doi:10.1097/00041552-200301000-00006]
Essig, M., Terzi, F., Burtin, M., Friedlander, G., 2001. Mechanical strains induced by tubular flow affect the phenotype of proximal tubular cells. Am. J. Physiol. Renal. Physiol., 281(4):F751–F762.
Fan, J.M., Ng, Y.Y., Hill, P.A., Nikolic-Paterson, D.J., Mu, W., Atkins, R.C., Lan, H.Y., 1999. Transforming growth factor-beta regulates tubular epithelial-myofibroblast transdifferentiation in vitro. Kidney Int., 56(4):1455–1467. [doi:10.1046/j.1523-1755.1999.00656.x]
Gnudi, L., Thomas, S.M., Viberti, G., 2007. Mechanical forces in diabetic kidney disease: a trigger for impaired glucose metabolism. J. Am. Soc. Nephrol., 18(8):2226–2232. [doi:10.1681/ASN.2006121362]
Hostetter, T.H., Olson, J.L., Rennke, H.G., Venkatachalam, M.A., 1981. Hyperfiltration in remnant nephrons: a potentially adverse response to renal ablation. Am. J. Physiol., 241(1):F85–F93.
Kaufman, J.M., Siegel, N.J., Hayslett, J.P., 1975. Functional and hemodynamic adaptation to progressive renal ablation. Circ. Res., 36(2):286–293.
Klahr, S., Schreiner, G., Ichikawa, I., 1988. The progression of renal disease. New Engl. J. Med., 318:1657–1666.
Lehoux, S., Castier, Y., Tedgui, A., 2006. Molecular mechanisms of the vascular responses to haemodynamic forces. J. Intern. Med., 259(4):381–392. [doi:10.1111/j.1365-2796.2006.01624.x]
Martin, J.S., Brown, L.S., Haberstroh, K.M., 2005. Microfilament are involved in renal responses to sustained hydrostatic pressure. J. Urol., 173(4):1410–1417. [doi:10.1097/01.ju.0000149031.93643.a5]
Maruyama, T., Hayashi, Y., Nakane, A., Sasaki, S., Kohri, K., 2005. Intermittent pressure-loading increases transforming growth factor-beta-1 secretion from renal tubular epithelial cells in vitro vesicoureteral reflux model. Urol. Int., 75(2):150–158. [doi:10.1159/000087170]
Meguid El Nahas, A., Bello, A.K., 2005. Chronic kidney disease: the global challenge. Lancet, 365(9456):331–340. [doi:10.1016/S0140-6736(05)17789-7]
Miyajima, A., Chen, J., Kirman, I., Poppas, D.P., Darracott Vaughan, E., Felsen, D., 2000. Interaction of nitric oxide and transforming growth factor-beta 1 induced by angiotensin II and mechanical stretch in rat renal tubular epithelial cells. J. Urol., 164(5):1729–1734. [doi:10.1016/S0022-5347(05)67097-8]
Mori, T., Cowley, A.W., 2004. Role of pressure in angiotensin II-induced renal injury chronic servo-control of renal perfusion pressure in rats. Hypertension, 43(4):752–759. [doi:10.1161/01.HYP.0000120971.49659.6a]
Ohashi, T., Sugaya, Y., Sakamoto, N., Sato, M., 2007. Hydrostatic pressure influences morphology and expression of VE-cadherin of vascular endothelial cells. J. Biomech., 40(11):2399–2405. [doi:10.1016/j.jbiomech.2006.11.023]
Palmer, J.S., Boyce, M.C., 2008. Constitutive modeling of the stress-strain behavior of F-actin filament networks. Acta Biomaterialia, 4(3):597–612. [doi:10.1016/j.actbio.2007.12.007]
Rodriguez-Pena, A., Prieto, M., Duwel, A., Rivas, J.V., Eleno, N., Perez-Barriocanal, F., Arevalo, M., Smith, J.D., Vary, C.P., Bernabeu, C., Lopez-Novoa, J.M., 2001. Up-regulation of endoglin, a TGF-β-binding protein, in rats with experimental renal fibrosis induced by renal mass reduction. Nephrol. Dial. Transplant., 16(Suppl. 1):34–39.
Sato, M., Muragaki, Y., Saika, S., Roberts, A.B., Ooshima, A., 2003. Targeted disruption of TGF-β1/Smad3 signaling protects against renal tubulointerstitial fibrosis induced by unilateral ureteral obstruction. J. Clin. Invest., 112(10):1486–1494. [doi:10.1172/JCI200319270]
Shin, H.Y., Gerritsen, M.E., Bizios, R., 2002. Regulation of endothelial cell proliferation and apoptosis by cyclic pressure. Ann. Biomed. Eng., 30(3):297–304. [doi:10.1114/1.1458595]
Silverman, M.D., Waters, C.R., Hayman, G.T., Wigboldus, J., Samet, M.M., Lelkes, P.I., 1999. Tissue factor activity is increased in human endothelial cells cultured under elevated static pressure. Am. J. Physiol. Cell Physiol., 277(2):233–242.
Suda, T., Osajima, A., Tamura, M., Kato, H., Iwamoto, M., Ota, T., Kanegae, K., Tanaka, H., Anai, H., Kabashima, N., Okazaki, M., Nakashima, Y., 2001. Pressure-induced expression of monocyte chemoattractant protein-1 through activation of MAP kinase. Kidney Int., 60(5):1705–1715. [doi:10.1046/j.1523-1755.2001.00012.x]
Wang, J.H.C., Thampatty, B.P., 2006. An introductory review of cell mechanobiology. Biomech. Model. Mechanobiol., 5(1):1–16. [doi:10.1007/s10237-005-0012-z]
Zavadil, J., Bottinger, E.P., 2005. TGF-beta and epithelial-to-mesenchymal transitions. Oncogene, 24(37):5764–5774. [doi:10.1038/sj.onc.1208927]
Zeisberg, M., Kalluri, R., 2004. The role of epithelial-to-mesenchymal transition in renal fibrosis. J. Mol. Med., 82(3):175–181. [doi:10.1007/s00109-003-0517-9]
Author information
Authors and Affiliations
Corresponding author
Additional information
The two authors contributed equally to this work
Project (No. 2007CB947802) supported by National Basic Research Program of China
Rights and permissions
About this article
Cite this article
Li, Fy., Xie, Xs., Fan, Jm. et al. Hydraulic pressure inducing renal tubular epithelial-myofibroblast transdifferentiation in vitro. J. Zhejiang Univ. Sci. B 10, 659–667 (2009). https://doi.org/10.1631/jzus.B0920110
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1631/jzus.B0920110
Key words
- Hydraulic pressure
- Tubular epithelial-myofibroblast transdifferentiation
- Transforming growth factor-β1 (TGF-β1)