| First Author | Chandran RR | Year | 2021 |
| Journal | Nat Commun | Volume | 12 |
| Issue | 1 | Pages | 7179 |
| PubMed ID | 34893592 | Mgi Jnum | J:358772 |
| Mgi Id | MGI:6842784 | Doi | 10.1038/s41467-021-27499-8 |
| Citation | Chandran RR, et al. (2021) Distinct roles of KLF4 in mesenchymal cell subtypes during lung fibrogenesis. Nat Commun 12(1):7179 |
| abstractText | 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)-beta(+) cells are the predominant source of myofibroblasts and Kruppel-like factor (KLF) 4 is upregulated in PDGFR-beta(+) cells, inducing TGFbeta pathway signaling and fibrosis. In fibrotic lung patches, KLF4 is down-regulated, suggesting KLF4 levels decrease as PDGFR-beta(+) cells transition into myofibroblasts. In contrast to PDGFR-beta(+) cells, KLF4 reduction in alpha-smooth muscle actin (SMA)(+) cells non-cell autonomously exacerbates lung fibrosis by inducing macrophage accumulation and pro-fibrotic effects of PDGFR-beta(+) 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-beta(+) cells and SMA(+) cells and highlight the importance of further studies of interactions between distinct mesenchymal cell types. |
