Distinct roles of KLF4 in mesenchymal cell subtypes during lung fibrogenesis.

ABSTRACT: During lung fibrosis, the epithelium induces signaling to underlying mesenchyme to generate excess myofibroblasts and extracellular matrix; herein, we focus on signaling in the mesenchyme. Our studies indicate that platelet-derived growth factor receptor (PDGFR)-β⁺ cells are the predominant source of myofibroblasts and Kruppel-like factor (KLF) 4 is upregulated in PDGFR-β⁺ cells, inducing TGFβ pathway signaling and fibrosis. In fibrotic lung patches, KLF4 is down-regulated, suggesting KLF4 levels decrease as PDGFR-β⁺ cells transition into myofibroblasts. In contrast to PDGFR-β⁺ cells, KLF4 reduction in α-smooth muscle actin (SMA)⁺ cells non-cell autonomously exacerbates lung fibrosis by inducing macrophage accumulation and pro-fibrotic

SUBMITTER: Chandran RR 

PROVIDER: S-EPMC8664937 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature