Hypoxia-induced microRNA-155 promotes fibrosis in proximal tubule cells

Abstract

Hypoxia has been considered to be a significant microenvironmental factor in promoting renal fibrosis, which causes progressive kidney disease and renal allograft failure. Previous studies have demonstrated versatile functions of miR-155 in hypoxia and fibrosis of the lung and liver. However, it is unclear whether miR-155 is able to regulate renal fibrosis and what the detailed mechanisms of this may be. In the current study, we focused on the interaction of miR-155/hypoxia-inducible factor 1 alpha (HIF-1α) and the effects of miR-155 on fibrosis in hypoxic HK-2 cells. Analysis of the expression of miR-155 and fibrosis-associated cytokines revealed upregulated miR-155, increased transforming growth factor beta 1 (TGF-β1) and alpha-smooth muscle actin, and decreased E-cadherin in hypoxic HK-2 cells. Further study demonstrated that miR-155 played a positive role in regulating HIF-1α and vice versa. Moreover, the data illustrated the synergistic effects of upregulated miR-155 on fibrosis by gain-of-function and loss-of-function methods in hypoxic HK-2 cells. Notably, the results also revealed that miR-155 had the ability to modulate TGF-β1 and the process of epithelial-mesenchymal transition (EMT). In conclusion, this study not only demonstrated that hypoxia-induced miR-155 was a pro-fibrotic cytokine which was positively regulated by HIF-1α, but also revealed that miR-155 promoted the fibrosis of proximal tubule cells by regulating both TGF-β1 and the process of EMT under hypoxia.