Cardiac Overexpression of Chil1 Improves Wound Healing to Prevent Cardiac Rupture After Myocardial Infarction
Cardiac Overexpression of Chil1 Improves Wound Healing to Prevent Cardiac Rupture After Myocardial Infarction
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DOI：
10.1007/s12265-022-10328-8
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发表时间：
2022-11
影响因子：
3.4
通讯作者：
Tianbao Ye;Boshen Yang;Peng Wei;Kaifan Niu;Taixi Li;Di Wang;Yaping Zhang;Yu Chen;Chengxing Shen;Xiaoqing Wang;Xian Jin;Liang Liu
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文献类型：
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作者：
Tianbao Ye;Boshen Yang;Peng Wei;Kaifan Niu;Taixi Li;Di Wang;Yaping Zhang;Yu Chen;Chengxing Shen;Xiaoqing Wang;Xian Jin;Liang Liu
及时形成富含胶原的瘢痕对预防心肌梗死后心室破裂具有重要意义。Chil 1（Chitinase 3-like 1）是一种与组织重塑反应相关的分泌蛋白。然而，其在MI进展中的功能仍然难以捉摸。心肌梗死后损伤区Chil 1表达下调。过表达Chil 1可显著减少心肌梗死后的心脏破裂，增加心肌壁厚度，并改善心肌功能，这是由于富含胶原的瘢痕形成和细胞外基质重塑。在体外，Chil 1诱导成纤维细胞转化为肌成纤维细胞。磷酸化蛋白质组学研究揭示了Chil 1与EGFR结合增强RAF/MEK 1/ERK信号通路发挥心脏保护作用的机制。与RAF抑制剂共同处理后，Chil 1对成纤维细胞转化和心肌保护的作用部分被取消。总之，我们的研究结果确定Chil 1通过与EGFR结合进一步激活RAF/MEK 1/ERK信号通路，在MI进展中作为保护因子。
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.Graphical abstract