胰岛素样生长因子结合蛋白-1调节缺氧心肌细胞中缺氧诱导因子-1α的降解以抑制细胞凋亡。

Insulin-like growth factor binding protein-1 regulates HIF-1α degradation to inhibit apoptosis in hypoxic cardiomyocytes.

作者信息

Tang Xiaoyan, Jiang Huilin, Lin Peiyi, Zhang Zhenhui, Chen Meiting, Zhang Yi, Mo Junrong, Zhu Yongcheng, Liu Ningning, Chen Xiaohui

机构信息

Department of Emergency, the Second Affiliated Hospital, Guangzhou Medical University, 510260, Guangzhou, Guangdong, China.

Guangzhou Institute of Cardiovascular Disease, Guangdong Key Laboratory of Vascular Diseases, State Key Laboratory of Respiratory Disease, the Second Affiliated Hospital, Guangzhou Medical University, 510260, Guangzhou, China.

出版信息

Cell Death Discov. 2021 Sep 16;7(1):242. doi: 10.1038/s41420-021-00629-3.

Hypoxia is important in ischemic heart disease. Excessive Insulin-like growth factor binding protein-1 (IGFBP-1) amounts are considered to harm cardiomyocytes in acute myocardial infarction. However, the mechanisms by which IGFBP-1 affects cardiomyocytes remain undefined. The present study demonstrated that hypoxia up-regulates IGFBP-1 and HIF-1α protein expression in cardiomyocytes. Subsequent assays showed that IGFBP-1 suppression decreased HIF-1α expression and inhibited hypoxia-induced apoptosis in cardiomyocytes, which was reversed by HIF-1α overexpression, indicating that HIF-1α is essential to IGFBP-1 function in cellular apoptosis. In addition, we showed that IGFBP-1 regulated HIF-1α stabilization through interacting with VHL. The present findings suggest that IGFBP-1-HIF-1α could be targeted for treating ischemic heart disease.

缺氧在缺血性心脏病中具有重要意义。过量的胰岛素样生长因子结合蛋白-1（IGFBP-1）被认为会在急性心肌梗死中损害心肌细胞。然而，IGFBP-1影响心肌细胞的机制仍不明确。本研究表明，缺氧可上调心肌细胞中IGFBP-1和HIF-1α蛋白的表达。随后的实验表明，抑制IGFBP-1可降低HIF-1α的表达，并抑制缺氧诱导的心肌细胞凋亡，而HIF-1α的过表达可逆转这种作用，这表明HIF-1α对于IGFBP-1在细胞凋亡中的功能至关重要。此外，我们还表明IGFBP-1通过与VHL相互作用来调节HIF-1α的稳定性。目前的研究结果表明，IGFBP-1-HIF-1α可能是治疗缺血性心脏病的靶点。