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HIF-1α contributes to Ang II-induced inflammatory cytokine production in podocytes

Abstract Background Studies have indicated that changed expression of hypoxia-inducible factor-1α (HIF-1α) in epithelial cells from the kidney could affect the renal function in chronic kidney disease (CKD). As Angiotensin II (Ang II) is a critical active effector in the renin-angiotensin system (RA...

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Main Authors: Hao Huang (Author), Yanqin Fan (Author), Zhao Gao (Author), Wei Wang (Author), Ning Shao (Author), Lu Zhang (Author), Yingjie Yang (Author), Weifang Zhu (Author), Zhaowei Chen (Author), Jijia Hu (Author), Guohua Ding (Author)
Format: Book
Published: BMC, 2019-10-01T00:00:00Z.
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Summary:Abstract Background Studies have indicated that changed expression of hypoxia-inducible factor-1α (HIF-1α) in epithelial cells from the kidney could affect the renal function in chronic kidney disease (CKD). As Angiotensin II (Ang II) is a critical active effector in the renin-angiotensin system (RAS) and was proved to be closely related to the inflammatory injury. Meanwhile, researchers found that Ang II could alter the expression of HIF-1α in the kidney. However, whether HIF-1α is involved in mediating Ang II-induced inflammatory injury in podocytes is not clear. Methods Ang II perfusion animal model were established to assess the potential role of HIF-1α in renal injury in vivo. Ang II stimulated podocytes to observe the corresponding between HIF-1α and inflammatory factors in vitro. Results The expression of inflammatory cytokines such as MCP-1 and TNF-α was increased in the glomeruli from rats treated with Ang II infusion compared with control rats. Increased HIF-1α expression in the glomeruli was also observed in Ang II-infused rats. In vitro, Ang II upregulated the expression of HIF-1α in podocytes. Furthermore, knockdown of HIF-1α by siRNA decreased the expression of MCP-1 and TNF-α. Moreover, HIF-1α siRNA significantly diminished the Ang II-induced overexpression of HIF-1α. Conclusion Collectively, our results suggest that HIF-1α participates in the inflammatory response process caused by Ang II and that downregulation of HIF-1α may be able to partially protect or reverse inflammatory injury in podocytes.
Item Description:10.1186/s40360-019-0340-8
2050-6511

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