Post-translational regulation of PGC-1α modulates fibrotic repair.

ABSTRACT: Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease associated with mitochondrial oxidative stress. Mitochondrial reactive oxygen species (mtROS) are important for cell homeostasis by regulating mitochondrial dynamics. Here, we show that IPF BAL cells exhibited increased mitochondrial biogenesis that is, in part, due to increased nuclear expression of peroxisome proliferator-activated receptor-ɣ (PPARɣ) coactivator (PGC)-1α. Increased PPARGC1A mRNA expression directly correlated with reduced pulmonary function in IPF subjects. Oxidant-mediated activation of the p38 MAPK via Akt1 regulated PGC-1α activation to increase mitochondrial biogenesis in monocyte-derived macrophages. Demonstrating the importance of PGC-1α in fibrotic repair, mice harboring a conditional deletion of Pp

SUBMITTER: Larson-Casey JL 

PROVIDER: S-EPMC8252570 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature