Timely formation of collagen-rich-scar is of importance to prevent ventricular rupture after myocardial infarction (MI). Chil1 (Chitinase 3-like 1) is a secreted protein associated with tissue remodeling response. However, its function in MI progression remains elusive. Chil1 was downregulated in the injured area overall post-MI. Overexpression of Chil1 markedly reduced cardiac rupture, increased wall thickness, and improved cardiac function post-MI due to collagen-rich-scar formation and extracellular matrix remodeling. In vitro, Chil1 induced the transformation of fibroblasts to myofibroblasts. Mechanistically, a phosphoproteomics study revealed that Chil1 binded to the EGFR enhancing RAF/MEK1/ERK signaling pathway to exert cardiac protection function. The effects of Chil1 on fibroblasts transformation and cardiac protections after MI were partially abolished by co-treated with RAF inhibitor. Together, our findings identify Chil1 as a protection factor in MI progression through binding to EGFR which further activates RAF/MEK1/ERK signaling pathway.
Keywords: Chil1; Collagen; EGFR pathway; Myocardial infarction; Wound healing.
© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.