Hsp90 and HIF-1α regulate mitophagy by promoting BNIP3 expression in renal ischemia-reperfusion injury

Ischemia-reperfusion injury (IRI) is a major cause of acute kidney injury (AKI). Studies have shown that mitochondrial damage is involved in the pathogenesis of AKI, and that inhibition of Hsp90 expression can improve IR-induced AKI. However, the mechanisms by which Hsp90 improves IR-induced AKI and whether it is involved in mitochondrial autophagy remain unclear.

An IR-induced AKI mouse model was established, and the degree of renal injury was analyzed using hematoxylin and eosin (H&E) and periodic acid-Schiff (PAS) staining. The expression of Hsp90, HIF-1α, BNIP3, and mitochondrial autophagy proteins was detected by western blotting in vivo and in vitro. HK2 cell viability, apoptosis, mitochondrial autophagy, reactive oxygen species (ROS), and inflammatory cytokines levels were detected using Cell Counting Kit 8 (CCK8) assays, Terminal·deoxynucleotidyl transferase-mediated dUTP nick end·labeling (TUNEL) labeling, immunofluorescence, and enzyme-linked immunosorbent (ELISA).

A murine IR-induced AKI model was successfully generated, and increased expression levels of Hsp90, HIF-1α, and inflammatory cytokines were observed, accompanied by a worsening of renal injury. After induction of IRI in HK2 cells, downregulation of Hsp90 or HIF-1α expression resulted in decreased downstream BNIP3 expression, an increase in HK2 cell viability, and a decrease in the level of mitochondrial autophagy.

Hsp90 upregulated the expression of HIF-1αand BNIP3, thereby enhancing mitochondrial autophagy in IR-induced AKI.