GLIS1 alleviates cell senescence and renal fibrosis through PGC1-α mediated mitochondrial quality control in kidney aging
Xu Li, Jiao Wang, Hongyuan Yu, Hang Mei, Ping He, Min Wang, Yue Liu, Qiuling Fan, Ying Chen, Yanqiu Li, Fan Liu
Abstract
Mitochondrial dysfunction is implied as a crucial factor in age-related chronic kidney disease. It is confirmed that Gli-like transcription factor 1 (GLIS1) is involved in age-related renal fibrosis, however, the correlation between mitochondrial disturbances and GLIS1-driven kidney aging are not clearly clarified. Thus, we investigated the regulatory mechanism of GLIS1 in the homeostasis of mitochondrial quality control both in vivo and in vitro. The lower expression of GLIS1 was identified in natural and accelerated kidney aged models, accompanied by the dysfunctions of mitochondrial quality control, including enhanced mitochondrial fission, reduced mitochondrial biogenesis and mitophagy, whereas, GLIS1 could maintain mitochondrial stability by interacting with peroxisome proliferator-activated receptor γ coactivator-1α (PGC1-α). Additionally, the over-expressed GLIS1 inhibited extracellular matrix accumulation and alleviated renal fibrosis while siGLIS1 inhibited PGC1-α transcription, as well as affecting its mitochondria-protective functions. Collectively, we demonstrated that GLIS1 mediated mitochondrial quality control through targeting PGC1-α in kidney aging, which might be a promising therapeutic target for attenuating cell senescence and age-related renal fibrosis.