Xiao Dan, Zhang Yue, Wang Rui, Fu Yujie, Zhou Tong, Diao Hongtao, Wang Zhixia, Lin Yuan, Li Zhange, Wen Lin, Kang Xujuan, Kopylov Philipp, Shchekochikhin Dmitri, Zhang Yong, Yang Baofeng
Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical University, Harbin 150081, China.
Department of Pharmacy, The First Affiliated Hospital of Harbin Medical University, Harbin 150081, China.
Acta Pharm Sin B. 2019 Jul;9(4):724-733. doi: 10.1016/j.apsb.2019.04.003. Epub 2019 Apr 22.
Excess activation of cardiac fibroblasts inevitably induces cardiac fibrosis. Emodin has been used as a natural medicine against several chronic diseases. The objective of this study is to determine the effects of emodin on cardiac fibrosis and the underlying molecular mechanisms. Intragastric administration of emodin markedly decreased left ventricular wall thickness in a mouse model of pathological cardiac hypertrophy with excess fibrosis induced by transaortic constriction (TAC) and suppressed activation of cardiac fibroblasts induced by angiotensin II (AngII). Emodin upregulated expression of metastasis associated protein 3 (MTA3) and restored the MTA3 expression in the setting of cardiac fibrosis. Moreover, overexpression of MTA3 promoted cardiac fibrosis; in contrast, silence of MTA3 abrogated the inhibitory effect of emodin on fibroblast activation. Our findings unraveled the potential of emodin to alleviate cardiac fibrosis upregulating MTA3 and highlight the regulatory role of MTA3 in the development of cardiac fibrosis.
心脏成纤维细胞的过度激活不可避免地会导致心脏纤维化。大黄素已被用作治疗多种慢性疾病的天然药物。本研究的目的是确定大黄素对心脏纤维化的影响及其潜在的分子机制。在经主动脉缩窄（TAC）诱导的伴有过度纤维化的病理性心脏肥大小鼠模型中，胃内给予大黄素可显著降低左心室壁厚度，并抑制血管紧张素II（AngII）诱导的心脏成纤维细胞激活。大黄素上调转移相关蛋白3（MTA3）的表达，并在心脏纤维化的情况下恢复MTA3的表达。此外，MTA3的过表达促进了心脏纤维化；相反，MTA3的沉默消除了大黄素对成纤维细胞激活的抑制作用。我们的研究结果揭示了大黄素通过上调MTA3来减轻心脏纤维化的潜力，并突出了MTA3在心脏纤维化发展中的调节作用。
