Department of Pathology and Forensic Medicine, College of Basic Medical Sciences, Dalian Medical University, Dalian, China.
J Cell Mol Med. 2019 Jun;23(6):4229-4243. doi: 10.1111/jcmm.14313. Epub 2019 Apr 14.
Transforming growth factor beta (TGFβ) plays a crucial role in tissue fibrosis. A number of studies have shown that TGFβ3 significantly attenuated tissue fibrosis. However, the mechanism involved in this effect is poorly understood. In this study we found that the expression level of TGFβ3 was higher in human myocardial infarction (MI) tissues than in normal tissues, and interestingly, it increased with the development of fibrosis post-myocardial infarction (post-MI). In vitro, human cardiac fibroblasts (CFs) were incubated with angiotensin II (Ang II) to mimic the ischaemic myocardium microenvironment and used to investigate the anti-fibrotic mechanism of TGFβ3. Then, fibrosis-related proteins were detected by Western blot. It was revealed that TGFβ3 up-regulation attenuated the proliferation, migration of human CFs and the expression of collagens, which are the main contributors to fibrosis, promoted the phenotype shift and the cross-linking of collagens. Importantly, the expression of collagens was higher in the si-smad7 groups than in the control groups, while silencing smad7 increased the phosphorylation level of the TGFβ/smad signalling pathway. Collectively, these results indicated that TGFβ3 inhibited fibrosis via the TGFβ/smad signalling pathway, possibly attributable to the regulation of smad7, and that TGFβ3 might serve as a potential therapeutic target for myocardial fibrosis post-MI.
转化生长因子-β（TGFβ）在组织纤维化中起着至关重要的作用。许多研究表明，TGFβ3 可显著减轻组织纤维化。然而，其作用机制尚不清楚。在本研究中，我们发现 TGFβ3 在人类心肌梗死（MI）组织中的表达水平高于正常组织，有趣的是，它随着心肌梗死后纤维化的发展（post-MI）而增加。在体外，用人心脏成纤维细胞（CFs）孵育血管紧张素 II（Ang II）模拟缺血性心肌微环境，用于研究 TGFβ3 的抗纤维化机制。然后，通过 Western blot 检测纤维化相关蛋白。结果表明，TGFβ3 的上调可减弱人 CFs 的增殖、迁移和胶原的表达，胶原是纤维化的主要贡献者，促进胶原的表型转变和交联。重要的是，si-smad7 组的胶原表达高于对照组，而沉默 smad7 可增加 TGFβ/smad 信号通路的磷酸化水平。综上所述，这些结果表明 TGFβ3 通过 TGFβ/smad 信号通路抑制纤维化，可能归因于 smad7 的调节，TGFβ3 可能成为心肌梗死后纤维化的潜在治疗靶点。
