Year: 2021
Type: article
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 effects of PDGFR-β+ cells via a Forkhead box M1 to C-C chemokine ligand 2—receptor 2 pathway. Taken together, in the context of lung fibrosis, our results indicate that KLF4 plays opposing roles in PDGFR-β+ cells and SMA+ cells and highlight the importance of further studies of interactions between distinct mesenchymal cell types.
Source: Nature Communications
Institution: Yale University
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $5,560
Awards: G1044130170, Mural cell TGF-beta-mediated signaling and neonatal intracerebral hemorrhage, CELL TYPE-SPECIFIC KLF4 REGULATION OF LUNG FIBROSIS, G3328267485, Smooth muscle progenitors in vascular remodeling, G412739762, G5260294809, G6310124767, G6556747164, G661160985, Pathological arterial muscularization and the role of integrins, G6819489701, Myofibroblasts in pulmonary fibrosis: origin, clones and KLF4, G7305545588, Novel vascular smooth muscle cell progenitors in development and disease, G8370089260, Mechanisms of reverse vascular remodeling in pulmonary hypertension, Yale Clinical and Translational Science Award
OpenAlex ID: W4200124452