Nicotinamide N-methyltransferase mediates lipofibroblast-myofibroblast transition and apoptosis resistance.

ABSTRACT: Metabolism controls cellular phenotype and fate. In this report, we demonstrate that nicotinamide N-methyltransferase (NNMT), a metabolic enzyme that regulates developmental stem cell transitions and tumor progression, is highly expressed in human idiopathic pulmonary fibrosis (IPF) lungs, and is induced by the pro-fibrotic cytokine, transforming growth factor-β1 (TGF-β1) in lung fibroblasts. NNMT silencing reduces the expression of extracellular matrix proteins, both constitutively and in response to TGF-β1. Furthermore, NNMT controls the phenotypic transition from homeostatic, pro-regenerative lipofibroblasts to pro-fibrotic myofibroblasts. This effect of NNMT is mediated, in part, by the downregulation of lipogenic transcription factors, TCF21 and PPARγ, and the induction of a less prol

SUBMITTER: Rehan M 

PROVIDER: S-EPMC10413354 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature