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SH2 domain-containing protein tyrosine phosphatase-2 (SHP-2) prevents cardiac remodeling after myocardial infarction through ERK/SMAD signaling pathway

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Abstract

In this study, we aimed to investigate the role of SH2 domain-containing protein tyrosine phosphatase-2 (SHP-2) in cardiac remodeling after myocardial infarction (MI) and explore the underlying molecular mechanism. MI model was established by ligation of the left anterior descending coronary artery. C57/BL6J mice were randomly administered with 3.0 mg/kg/day PHPS1 (PHPS1-treated group) or normal saline (model group) by intraperitoneal injection. After 4 weeks of infusion, the effects of PHPS1 on cardiac remodeling were evaluated. Echocardiography results showed that PHPS1 treatment aggravated the MI-induced deterioration of cardiac function, with worse cardiac function parameters. PHPS1 treatment significantly increased the infarcted area, as well as the fibrotic area and the expression of collagen I and collagen III. Western blots and immunofluorescence staining showed that PHPS1 treatment up-regulated the expression of p-GRK2, p-SMAD2/3 and p-ERK1/2, while U0126 reversed the effect of PHPS1. The present study indicated that PHPS1 treatment contributed to myocardial fibrosis and infarction by activating ERK/SMAD signaling pathway, suggesting that SHP-2 may be a promising treatment target for cardiac remodeling after MI.

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Data availability statement

All data generated or analysed during this study are included in this published article [and its supplementary information files].

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Funding

This work was supported by Prevention and Control of Geriatric Diseases in 2018 [number 2018135809-2].

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Authors and Affiliations

  1. Department of Clinical Laboratory, Hebei General Hospital, No. 348, Heping Road, Xinhua District, Shijiazhuang, 050051, China

    Yong-Gang Lu, He Tan, Qian Ma, Xin-Xin Li, Jia Cui & Yan-Qing Tie

  2. Department of Clinical Laboratory, Hebei North University, Zhangjiakou, China

    Xue Zhang & Xue-Lei Liang

Authors
  1. Yong-Gang Lu
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  2. He Tan
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  3. Qian Ma
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  4. Xin-Xin Li
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Contributions

Conception and design, YT and YL; Data collection, YL, HT, QM and XL; Data analysis and interpretation, JC and XZ; Drafting article, YL, XL and YT; Administrative support, YT. All the authors have read and approved the final manuscript.

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Correspondence to Yan-Qing Tie.

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All animal experiments were performed in accordance with the guidelines for animal care and the experimental protocols were approved by the Institutional Animal Care and Use Committee of our hospital.

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Lu, YG., Tan, H., Ma, Q. et al. SH2 domain-containing protein tyrosine phosphatase-2 (SHP-2) prevents cardiac remodeling after myocardial infarction through ERK/SMAD signaling pathway. Human Cell 34, 325–334 (2021). https://doi.org/10.1007/s13577-020-00430-x

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