Transforming growth factor beta 1 inhibits proliferation of human renal tubular epithelial cells

doi:10.3969/j.issn.2095-4344.2013.07.016

Abstract

Abstract:

BACKGROUND: An important pathological change in the progression of chronic renal failure means inflammation and fibrosis, including glomerular and tubular inflammation and fibrosis. At present, most of the research has focused on the glomerulus rather than renal tubular lesions. But actually, for a part of diseases, renal tubular lesions appear before glomerular lesions, which is of more guiding significance for the prognosis of diseases.
OBJECTIVE: To observe the effect of transforming growth factor beta 1 on the cell proliferation of HK-cells and to explore the role of transforming growth factor beta 1 in renal tubular inflammation and fibrosis.
METHODS: HK-2 cells were cultured in Dulbecco’s modified Eagle’s medium/F12 or Dulbecco’s modified Eagle’s medium/F12 containing different concentrations of transforming growth factor beta 1. HK-2 cells were divided into four groups, control group, 2 μg/L transforming growth factor beta 1 group, 5 μg/L transforming growth factor beta 1 group and 10 μg/L transforming growth factor beta 1 group. Morphological changes were assessed by inverted phase contrastmicroscopy and cellular proliferation was detected by MTT assay.
RESULTS AND CONCLUSION: The morphology of HK-2 cells changed from epithelial cobblestone to myofibroblast-like elongated and spindly and gap among cells also widened. The proliferation of HK-2 cells was inhibited significantly by transforming growth factor beta 1, but not in a dose-dependent manner. The inhibitory effect on the cellular proliferation lasted for 72 hours. These findings indicate that transforming growth factor beta 1 inhibits the cellular proliferation of HK-2 cells and promotes the occurrence of renal interstitial fibrosis.

Key words: tissue construction, tissue construction and bioactive factors, human renal tubular epithelial cells, inhibition of proliferation, transforming growth factor beta 1, fibrosis, HK-2 cells, cell proliferation, cell morphology, renal tubule, epithelial cells, tissue construction photographs-containing paper

CLC Number:

R318

Chen Yu-min, Xiong Zu-ying. Transforming growth factor beta 1 inhibits proliferation of human renal tubular epithelial cells[J]. Chinese Journal of Tissue Engineering Research, 2013, 17(7): 1228-1232.

Figures/Tables 4

References

[1] Bandara JM, Wijewardena HV, Liyanege J,et al. Chronic renal failure in Sri Lanka caused by elevated dietary cadmium: Trojan horse of the green revolution.Toxicol Lett. 2010;198(1): 33-39.

[2] Feest T. Epidemiology and causes of chronic renal failure. Medicine. 2007;35(8):438-441.

[3] Li DQ, Wang Y, Zhou GL,et al.Zhonghua Tangniaobing Zazhi. 2004;12(3): 219-224. 李丹清,王颖,周桂玲,等. 糖尿病肾病大鼠肾小管与肾小球病变的顺序及其意义[J].中华糖尿病杂志,2004,12(3): 219-224.

[4] Hertig A.Epithelial-mesenchymal transition of the renal graft. Nephrol Ther. 2008;4 Suppl 1:S25-S28.

[5] Ding Z, Chen Z, Chen X,et al. Adenovirus-mediated anti-sense ERK2 gene therapy inhibits tubular epithelial-mesenchymal transition and ameliorates renal allograft fibrosis.Transpl Immunol. 2011;25(1):34-41.

[6] Yoshino J, Monkawa T, Tsuji M,et al. Snaill is involved in the renal epithelial-mesenchymal transition. Biochem Biophys Res Commun. 2007;362(1):63-68.

[7] Margetts PJ, Bonniaud P, Liu L,et al.Transient overexpression of TGF-{beta}1 induces epithelial mesenchymal transition in the rodent peritoneum. J Am Soc Nephrol. 2005;16(2): 425-436.

[8] Thiery JP, Acloque H, Huang RY,et al. Epithelial-mesenchymal transitions in development and disease. Cell. 2009;139(5):871-890.

[9] Xu J, Lamouille S, Derynck R.TGF-beta-induced epithelial to mesenchymal transition.Cell Res. 2009;19(2):156-172.

[10] Kalluri R, Weinberg RA.The basics of epithelial-mesenchymal transition. J Clin Invest. 2009;119(6):1420-1428.

[11] Wang W, Koka V, Lan HY.Transforming growth factor-beta and Smad signalling in kidney diseases.Nephrology (Carlton). 2005;10(1):48-56.

[12] Lü L, Zhang L, Wai MS,et al. Exocytosis of MTT formazan could exacerbate cell injury.Toxicol In Vitro. 2012;26(4): 636-644.

[13] Kutz SM, Higgins CE, Samarakoon R,et al. TGF-beta 1-induced PAI-1 expression is E box/USF-dependent and requires EGFR signaling. Exp Cell Res. 2006;312(7): 1093-1105.

[14] Yang LX,Li Y,Wang Q,et al. Zhongguo Zhongxiyi Jiehe Zazhi. 2008;9(12): 1040-1043. 杨丽霞,李彧,王谦,等. 姜黄素对TGF-β1诱导人肾小管上皮细胞转分化及分泌细胞外基质成分的影响[J]. 中国中西医结合肾病杂志,2008,9(12): 1040-1043.

[15] Dudas PL, Argentieri RL, Farrell FX. BMP-7 fails to attenuate TGF-beta1-induced epithelial-to-mesenchymal transition in human proximal tubule epithelial cells. Nephrol Dial Transplant. 2009;24(5):1406-1416.