Figure 8.

Hypoxia-induced Twist1-PGC-1α axis mediated mitochondrial lipid metabolism contributes to progressive renal interstitial fibrosis. We found that Twist1 increased under chronic hypoxia and pathogenic conditions, leading to mitochondrial dysfunction and intracellular lipid accumulation and defective FAO by inhibiting PGC-1α and the downstream target genes PPARα, CPT1 and ACOX1. This, in turn, leads to ATP depletion and triglyceride overload and consequently facilitates lipotoxicity-induced TIF.