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.

在本研究中，我们旨在探讨含SH2结构域的蛋白酪氨酸磷酸酶2（SHP-2）在心肌梗死（MI）后心脏重塑中的作用，并探讨其潜在的分子机制。结扎左冠状动脉前降支建立MI模型。 C57/BL6J小鼠随机腹腔注射3.0 mg/kg/天PHPS1（PHPS1治疗组）或生理盐水（模型组）。输注4周后，评估PHPS1对心脏重塑的影响。超声心动图结果显示，PHPS1治疗加剧了MI引起的心功能恶化，心功能参数更差。 PHPS1治疗显着增加了梗塞面积、纤维化面积以及胶原蛋白I和胶原蛋白III的表达。蛋白质印迹和免疫荧光染色显示 PHPS1 处理上调了 p-GRK2、p-SMAD2/3 和 p-ERK1/2 的表达，而 U0126 逆转了 PHPS1 的作用。本研究表明PHPS1治疗通过激活ERK/SMAD信号通路导致心肌纤维化和梗死，这表明SHP-2可能是MI后心脏重构的有前景的治疗靶点。