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

ABSTRACT: BACKGROUND:Studies have indicated that changed expression of hypoxia-inducible factor-1? (HIF-1?) 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-1? in the kidney. However, whether HIF-1? 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-1? in renal injury in vivo. Ang II stimulated podocytes to observe the corresponding between HIF-1? and inflammatory factors in vitro. RESULTS:The expression of inflammatory cytokines such as MCP-1 and TNF-? was increased in the glomeruli from rats treated with Ang II infusion compared with control rats. Increased HIF-1? expression in the glomeruli was also observed in Ang II-infused rats. In vitro, Ang II upregulated the expression of HIF-1? in podocytes. Furthermore, knockdown of HIF-1? by siRNA decreased the expression of MCP-1 and TNF-?. Moreover, HIF-1? siRNA significantly diminished the Ang II-induced overexpression of HIF-1?. CONCLUSION:Collectively, our results suggest that HIF-1? participates in the inflammatory response process caused by Ang II and that downregulation of HIF-1? may be able to partially protect or reverse inflammatory injury in podocytes.

SUBMITTER: Huang H 

PROVIDER: S-EPMC6796393 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature