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Parthenolide ameliorates tweak-induced podocytes injury

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Abstract

Parthenolide (PTL) is a natural product from the shoots of Tanacetum parthenium, which has immunomodulatory effects in multiply type of diseases. This study aimed to explore the effect and the underlying mechanism of PTL on the anti-apoptotic and anti- inflammatory ability of tweak-induced podocytes. Conditionally immortalized mouse podocytes were incubated with Tumor necrosis factor-like weak inducer of apoptosis (Tweak, 100 ng/ml), PTL(10 µM) or Tweak + PTL for 12 h, 24 and 48 h, respectively. Podocytes viability was detected by CCK-8 assay. Tweak and Cxcl16 expression were evaluated by western blot and immunofluorescence assay. Dil-oxLDL stain was detected by immunofluorescence analysis. Intracellular Total Cholesterol (TC) content was measured through TC detection Kit. These results demonstrated that the podocytes cells viability was gradually decreased after treatment with different concentrations of Tweak (0, 50, 100, 150). Tweak and Cxcl16 protein expression in mouse podocytes treated with tweak were remarkably elevated and were found to have higher intracellular lipid accumulation compared with the control group, whereas co-administration with PTL, tweak and Cxcl16 expression as well as the intracellular lipid accumulation were notablely decreased in tweak-induced podocytes. Therefore, our conclusion was that tweak and Cxcl16 were involved in the regulation of tweak-induced podocytes injury. Meanwhile, the anti-apoptotic and anti-inflammatory effect of PTL may be correlated with the tweak and Cxcl16 expression decreased.

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References

  1. Bukosza EN, Kornauth C, Hummel K, Schachner H, Huttary N, Krieger S, Nöbauer K, Oszwald A, Razzazi Fazeli E, Kratochwill K, Aufricht C, Szénási G, Hamar P, Gebeshuber CA (2020) ECM characterization reveals a massive activation of acute phase response during FSGS. Int J Mol Sci 21(6):2095

    PubMed Central  Google Scholar 

  2. Rinschen MM, Huesgen PF, Koch RE (2018) The podocyte protease web: uncovering the gatekeepers of glomerular disease. Am J Physiol Renal Physiol 315(6):F1812–F1816

    CAS  PubMed  Google Scholar 

  3. Che G, Gao H, Hu Q, Xie H, Zhang Y (2020) Angiotensin II promotes podocyte injury by activating Arf6-Erk1/2-Nox4 signaling pathway. PLoS ONE 15(3):e0229747

    CAS  PubMed  PubMed Central  Google Scholar 

  4. Barisoni L, Mundel P (2003) Podocyte biology and the emerging understanding of podocyte diseases. Am J Nephrol 23:353–360

    PubMed  Google Scholar 

  5. Fuseya S, Suzuki R, Okada R, Hagiwara K, Sato T, Narimatsu H, Yokoi H, Kasahara M, Usui T, Morito N, Yamagata K, Kudo T, Takahashi S (2020) Mice lacking core 1-derived O-glycan in podocytes develop transient proteinuria, resulting in focal segmental glomerulosclerosis. Biochem Biophys Res Commun 523(4):1007–1013

    CAS  PubMed  Google Scholar 

  6. Cybulsky AV (2011) Membranous nephropathy. Contrib Nephrol 169:107–125

    CAS  PubMed  Google Scholar 

  7. Xu L, Yang HC, Hao CM, Lin ST, Gu Y, Ma J (2010) Podocyte number predicts progression of proteinuria in IgA nephropathy. Mod Pathol 23:1241–1250

    CAS  PubMed  Google Scholar 

  8. Keisuke S, Kohei M, Takuji E, Tomoki M, Yuichi M, Rina O, Tsukasa T, Mitsuru O (2020) Role of cathepsin L in idiopathic nephrotic syndrome in children. Med Hypotheses 141:109718

    CAS  PubMed  Google Scholar 

  9. Bollain-Y-Goytia JJ, Gonza´lez-Castaneda M, Torres-Del-Muro F, Daza-Benitez L, Zapata-Benavides P et al (2011) Indian J Nephrol 21:166–171

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Cambruzzi E, Pêgas KL (2019) Pathogenesis, histopathologic findings and treatment modalities of lipoprotein glomerulopathy: a review. J Bras Nefrol 41(3):393–399

    PubMed  Google Scholar 

  11. Cassis P, Zoja C, Perico L, Remuzzi G (2019) A preclinical overview of emerging therapeutic targets for glomerular diseases. Expert Opin Ther Targets 23(7):593–606

    CAS  PubMed  Google Scholar 

  12. Justo P, Sanz AB, Sanchez-Niño MD, Winkles JA, Lorz C, Egido J, Ortiz A (2006) Cytokine cooperation in renal tubular cell injury: the role of TWEAK. Kidney Int 70:1750–1758

    CAS  PubMed  Google Scholar 

  13. Chung AC, Lan HY (2011) Chemokines in renal injury. J Am Soc Nephrol 22:802–809

    CAS  PubMed  Google Scholar 

  14. Ludwig A, Weber C (2007) Transmembrane chemokines: versatile ‘special agents’ in vascular inflammation. Thromb Haemost 97:694–703

    CAS  PubMed  Google Scholar 

  15. Koziolek MJ, Vasko R, Bramlage C, Müller GA, Strutz F (2009) The CX(3) C-chemokine fractalkine in kidney diseases. Mini Rev Med Chem 9:1215–1228

    CAS  PubMed  Google Scholar 

  16. Wang L, Yao X, Li Q, Sun S (2018) Effect of simvastatin on lipid accumulation and the expression of CXCL16 and nephrin in podocyte induced by oxidized LDL. J Invest Surg 31(2):69–74

    CAS  PubMed  Google Scholar 

  17. Luo R, Yang Y, Cheng YC, Chang D, Liu TT, Li YQ, Dai W, Zuo MY, Xu YL, Zhang CX, Ge SW, Xu G (2020) Plasma chemokine CXC motif-ligand 16 as a predictor of renal prognosis in immunoglobulin A nephropathy. Ann Transl Med 8(6):381

    PubMed  PubMed Central  Google Scholar 

  18. He D, Hu J, Yang R, Zeng B, Yang D, Li D, Zhang M, Yang M, Ni Q, Ning R, Fan X, Li X, Mao X, Li Y (2020) Evolutionary analysis of chemokine CXCL16 and its receptor CXCR6 in murine rodents. Dev Comp Immunol 109:103718

    CAS  PubMed  Google Scholar 

  19. Hu ZB, Ma KL, Zhang Y, Wang GH, Liu L, Lu J, Chen PP, Lu CC, Liu BC (2018) Inflammation-activated CXCL16 pathway contributes to tubulointerstitial injury in mouse diabetic nephropathy. Acta Pharmacol Sin 39(6):1022–1033

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Liang H, Liao M, Zhao W, Zheng X, Xu F, Wang H, Huang J (2018) CXCL16/ ROCK1 signaling pathway exacerbates acute kidney injury induced by ischemia- reperfusion. Biomed Pharmacother 98:347–356

    CAS  PubMed  Google Scholar 

  21. Ruiz-Ortega M, Ortiz A, Ramos AM (2014) Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) and kidney disease. Curr Opin Nephrol Hypertens 23(1):93–100

    CAS  PubMed  Google Scholar 

  22. Yue Q, Gao G, Zou G, Yu H, Zheng X (2017) Natural products as adjunctive treatment for pancreatic cancer: recent trends and advancements. Biomed Res Int 2017:8412508

    PubMed  PubMed Central  Google Scholar 

  23. Sun J, Zhang C, Bao YL, Wu Y, Chen ZL, Yu CL, Huang YX, Sun Y, Zheng LH, Wang X, Li YX (2014) Parthenolide-induced apoptosis, autophagy and suppression of proliferation in HepG2 cells. Asian Pac J Cancer Prev 15:4897–4902

    PubMed  Google Scholar 

  24. Uchibori R, Tsukahara T, Ohmine K, Ozawa K (2014) Cancer gene therapy using mesenchymal stem cells. Int J Hematol 99:377–382

    CAS  PubMed  Google Scholar 

  25. Peng S, Hu C, Liu X, Lei L, He G, Xiong C, Wu W (2020) Rhoifolin regulates oxidative stress and proinflammatory cytokine levels in Freund’s adjuvant-induced rheumatoid arthritis via inhibition of NF-κB. Braz J Med Biol Res. https://doi.org/10.1590/1414-431x20209489

    Article  PubMed  PubMed Central  Google Scholar 

  26. Diamanti P, Cox CV, Moppett JP, Blair A (2013) Parthenolide eliminates leukemia-initiating cell populations and improves survival in xenografts of childhood acute lymphoblastic leukemia. Blood 121:1384–1393

    CAS  PubMed  Google Scholar 

  27. Al Fatlawi AA, Al-Fatlawi AA, Irshad M, Rahisuddin, Ahmad A (2015) Effect of parthenolide on growth and apoptosis regulatory genes of human cancer cell lines. Pharm Biol 53:104–109

    CAS  PubMed  Google Scholar 

  28. Sang WK, Park ES, Lee CS (2013) Parthenolide induces apoptosis by activating the mitochondrial and death receptor pathways and inhibits FAK-mediated cell invasion. Mol Cell Biochem 385:133–144

    Google Scholar 

  29. Ren Y, Li Y, Lv J, Guo X, Zhang J, Zhou D, Zhang Z, Xue Z, Yang G, Xi Q, Liu H, Liu Z, Zhang L, Zhang Q, Yao Z, Zhang R, Da Y (2019) Parthenolide regulates oxidative stress-induced mitophagy and suppresses apoptosis through p53 signaling pathway in C2C12 myoblasts. J Cell Biochem 120(9):15695–15708

    CAS  PubMed  Google Scholar 

  30. Hao QF, Wang BB, Zhang W, Qiu W, Liu QL, Li XM (2020) NF-κB inhibitor parthenolide promotes renal tubules albumin uptake in type 2 diabetic nephropathy. Chin Med Sci J 35(1):31–42

    PubMed  Google Scholar 

  31. Scheuer H, Gwinner W, Hohbach J, Gröne EF, Brandes RP, Malle E, Olbricht CJ, Walli AK, Gröne HJ (2000) Oxidant stress in hyperlipi-demia-induced renal damage. Am J Physiol Renal Physiol 278:F63–F74

    CAS  PubMed  Google Scholar 

  32. Singh S, Wu T, Xie C, Vanarsa K, Han J, Mahajan T, Oei HB, Ahn C, Zhou XJ, Putterman C, Saxena R, Mohan C (2012) Urine VCAM-1 as a marker of renal pathology activity index in lupus nephritis. Arthritis Res Ther 14(4):R164

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Izquierdo MC, Sanz AB, Mezzano S, Blanco J, Carrasco S, Sanchez-Niño MD, Benito-Martín A, Ruiz-Ortega M, Egido J, Ortiz A (2012) TWEAK (tumor necrosis factor-like weak inducer of apoptosis) activates CXCL16 expression during renal tubulointerstitial inflammation. Kidney Int 81(11):1098–107

    CAS  PubMed  Google Scholar 

  34. Zhang Y, Huang Q, Chen Y, Peng X, Wang Y, Li S, Wu J, Luo C, Gong W, Yin B, Xiao J, Zhou W, Peng F, Long H (2020) Parthenolide, an NF-κB inhibitor, alleviates peritoneal fibrosis by suppressing the TGF-β/Smad pathway. Int Immunopharmacol 78:106064

    CAS  PubMed  Google Scholar 

  35. Valiño-Rivas L, Cuarental L, Grana O, Bucala R, Leng L, Sanz A, Gomez G, Ortiz A, Sanchez-Niño MD (2018) TWEAK increases CD74 expression and sensitizes to DDT proinflammatory actions in tubular cells. PLoS ONE 13(6):e0199391

    PubMed  PubMed Central  Google Scholar 

  36. Sanz AB, Sanchez-Niño MD, Ortiz A (2011) TWEAK, a multi- functional cytokine in kidney injury. Kidney Int 80:708–718

    CAS  PubMed  Google Scholar 

  37. Moreno JA, Izquierdo MC, Sanchez-Niño MD, Suarez-Alvarez B, Lopez-Larrea C, Jakubowski A, Blanco J, Ramirez R, Selgas R, Ruiz-Ortega M, Egido J, Ortiz A, Sanz AB (2011) The inflammatory cytokines TWEAK and TNF-αreduce renal klotho expression through NF-κB. J Am Soc Nephrol 22:1315–1325

    CAS  PubMed  PubMed Central  Google Scholar 

  38. Sanz AB, Izquierdo MC, Sanchez-Niño MD, Ucero AC, Egido J, Ruiz-Ortega M, Ramos AM, Putterman C, Ortiz A (2014) TWEAK and the progression of renal disease: clinical translation. Nephrol Dial Transplant 29(Suppl 1):i54–i62

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Ruiz-Andres O, Suarez-Alvarez B, Sa´nchez-Ramos C, Monsalve M, Sanchez- Niño MD, Ruiz-Ortega M, Egido J, Ortiz A, Sanz AB (2016) The inflammatory cytokine TWEAK decreases PGC-1αexpression and mitochondrial function in acute kidney injury. Kidney Int 89:399–410

    CAS  PubMed  Google Scholar 

  40. Xia Y, Herlitz LC, Gindea S, Wen J, Pawar RD, Misharin A, Perlman H, Wu L, Wu P, Michaelson JS, Burkly LC, Putterman C (2015) Deficiency of fibroblast growth factor-inducible 14 (Fn14) preserves the filtration barrier and ameliorates lupus nephritis. J Am Soc Nephrol 26:1053–1070

    CAS  PubMed  Google Scholar 

  41. Gao HX, Campbell SR, Burkly LC, Jakubowski A, Jarchum I, Banas B, Saleem MA, Mathieson PW, Berman JW, Michaelson JS, Putterman C (2009) TNF-like weak inducer of apoptosis (TWEAK) induces inflammatory and proliferative effects in human kidney cells. Cytokine 46:24–35

    CAS  PubMed  Google Scholar 

  42. Chang TT, Chen JW (2020) The role of chemokines and chemokine receptors in diabetic nephropathy. Int J Mol Sci 21(9):E3172

    PubMed  Google Scholar 

  43. Wang D, Chen X, Fu M, Xu H, Li Z (2019) Tacrolimus increases the expression level of the chemokine receptor CXCR2 to promote renal fibrosis progression. Int J Mol Med 44(6):2181–2188

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Anders HJ, Vielhauer V, Schlondorff D (2003) Chemokines and chemokine receptors are involved in the resolution or progression of renal disease. Kidney Int 63:401–415

    CAS  PubMed  Google Scholar 

  45. Sugiyama M, Kinoshita K, Funauchi M (2015) The pathogenic role of macrophage in lupus nephritis. Nihon Rinsho Meneki Gakkai Kaishi 38(3):135

    CAS  PubMed  Google Scholar 

  46. Perez DL, Maier H, Nieto E, Vielhauer E, Luckow V, Mampaso B, Schlondorff F (2001) Chemokine expression precedes inflammatory cell infiltration and chemokine receptor and cytokine expression during the initiation of murine lupus nephritis. J Am Soc Nephrol 12:1369–1382

    Google Scholar 

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Acknowledgements

This work is funded by the Natural Science Foundation of Shandong Province (ZR2015HM009) and Shandong Key R&D Program (2017 GSF218005).

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Authors and Affiliations

  1. Department of Pediatric Nephrology and Rheumatism and Immunology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250021, People’s Republic of China

    Lichun Yu, Caihui Zhang & Shuzhen Sun

  2. Department of Pediatric Nephrology and Rheumatism and Immunology, Shandong Provincial Hospital Affiliated to Shandong First Medicial University, No 324 Jing Wu Road, Jinan, 250021, People’s Republic of China

    Lichun Yu, Yuan Chen, Qian Li, Jing Wang & Shuzhen Sun

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  1. Lichun Yu
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Correspondence to Shuzhen Sun.

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Yu, L., Zhang, C., Chen, Y. et al. Parthenolide ameliorates tweak-induced podocytes injury. Mol Biol Rep 47, 5165–5173 (2020). https://doi.org/10.1007/s11033-020-05591-4

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