The mechanism and therapeutic prospect of HIF-1 α/BNIP3 pathway in regulating mitophagy in tubulointerstitial fibrosis.
Tubulointerstitial fibrosis (TIF) is a key pathological hallmark and a major determinant of end-stage renal disease (ESRD). The mechanisms of TIF remain unclear, and there are currently no specific drugs to slow or reverse its progression. Notably, due to the kidney's unique structure, the course of renal dysfunction is intimately connected with hypoxia. The signaling pathway formed by hypoxia-inducible factor 1α (HIF-1α) and its downstream target gene, B-cell lymphoma-2/adenovirus E1B 19-kDa interacting protein (BNIP3), exerts a pivotal effect during renal hypoxia. This pathway mediates mitophagy, inhibits apoptosis and inflammatory responses, maintains cellular energy balance, and thus profoundly influences the progression of TIF. This article focuses on the molecular mechanism by which the HIF-1α/BNIP3 pathway regulates mitophagy and affects TIF, and delves into its mechanisms in pyroptosis, oxidative stress, and ischemia-reperfusion injury, This work endeavors to establish a theoretical foundation and potential intervention targets for developing novel treatment strategies for TIF.