2. Academic Validation
  3. Lefty1 Ameliorates Post-infarction Fibrosis by Suppressing p-Smad2 and p-ERK1/2 Signaling Pathways

Lefty1 Ameliorates Post-infarction Fibrosis by Suppressing p-Smad2 and p-ERK1/2 Signaling Pathways

  • J Cardiovasc Transl Res. 2021 Aug;14(4):636-646. doi: 10.1007/s12265-020-10089-2.
Chang-Yi Li 1 2,  Jing-Rui Zhang 1,  Xin-Xin Li 3,  Lei Zhao 4,  Hui Xi 5,  Wan-Ning Hu 6,  Song-Nan Li 7
Affiliations

Affiliations

  • 1 Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, No. 2, Anzhen Road, Chao Yang District, Beijing, 100029, China.
  • 2 Laboratory of Molecular Biology, Head and Neck Surgery, Tangshan Gongren Hospital, No. 27, Wenhua Road, Lubei District, Tangshan, 063000, China.
  • 3 Department of Respiratory Medicine, Tangshan People's Hospital, Tangshan, China.
  • 4 Department of Radiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China.
  • 5 Department of Cardiology, Peking University International Hospital, Beijing, China.
  • 6 Laboratory of Molecular Biology, Head and Neck Surgery, Tangshan Gongren Hospital, No. 27, Wenhua Road, Lubei District, Tangshan, 063000, China. huwanning1212@sina.com.
  • 7 Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, No. 2, Anzhen Road, Chao Yang District, Beijing, 100029, China. lisongnan@ccmu.edu.cn.
PMID: 33409963 DOI: 10.1007/s12265-020-10089-2
Abstract

Transforming growth factor-β1 signaling pathways are known to involve in the development of post-infarction fibrosis, a process characterized by the aberrant activation, proliferation, and differentiation of fibroblasts, as well as the unbalanced turnover of extracellular matrix proteins. Recent studies have shown that Lefty1, a novel member of TGF-β superfamily, acts as a brake on the TGF-β signaling pathway in non-cardiac tissues. However, its role in myocardial infarction (MI)-induced fibrosis and left ventricular remodeling has not been fully elucidated. Here, for the first time, we reported that Lefty1 alleviated post-MI fibroblast proliferation, differentiation, and secretion through suppressing p-Smad2 and p-ERK1/2 signaling pathways in vivo and in vitro. In MI mice or TGF-β1-treated neonatal rat cardiac fibroblasts (CFBs), the expression of Lefty1 was upregulated. Adenovirus-mediated overexpression of Lefty1 significantly attenuated TGF-β1-induced CFBs' proliferation, differentiation, and collagen production. Using the adeno-associated virus approach, we confirmed that Lefty1 attenuates MI-induced cardiac injury, as evidenced by the decreased infarct size and preserved cardiac function. These results highlight the importance of Lefty1 in the prevention of post-MI fibrosis and may help identify potential targets for therapeutic intervention of cardiac fibrosis. Graphical abstract.

Keywords

Cardiac remodeling; Lefty1; Myocardial fibrosis; Myocardial infarction; Transforming growth factor-β1.

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