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

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.