
The study uncovers how mesenchymal progenitor cells (MPCs) in idiopathic pulmonary fibrosis (IPF) evade negative regulation of self-renewal. The CD44/Brg1/PRMT5 module represses tumor suppressor genes RBL1 and PTEN in IPF MPCs. The mechanism involves the chromatin remodeler Brg1 binding to PRMT5, which methylates histones H3R8 and H4R3 on the RBL1 and PTEN genes, reducing their expression. Genetic knockdown or pharmacological inhibition of Brg1 or PRMT5 restored RBL1 and PTEN expression, reduced IPF MPC self-renewal in vitro, and inhibited IPF MPC-mediated fibrosis in vivo. This study highlights how this epigenetic module promotes self-renewal and fibrogenicity in IPF, driving relentless fibrosis progression.
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