Department of Cardiology, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, China.
Anal Cell Pathol (Amst). 2022 Mar 31;2022:5242323. doi: 10.1155/2022/5242323. eCollection 2022.
The activation of activin receptor-like kinase 4 (ALK4) signaling plays a pivotal role in the pressure-overloaded heart, and haplodeficiency of ALK4 can alleviate cardiac fibrosis secondary to myocardial infarction and preserve cardiac function through partially inactivating the Smad3/4 pathway. However, whether transforming growth factor (TGF) signaling is involved in the beneficial effects of ALK4 knockdown on the ischemic heart is still unclear. This study was undertaken to investigate the change in the TGF signaling after ALK4 knockdown and in vitro. Forty C57BL/6J mice were randomized into ALK4 ischemia/reperfusion (I/R) group (ALK4+I/R, = 10), ALK4 sham group (ALK4+sham, = 10), wild-type sham group (WT+sham, = 10), and WT I/R group (WT+I/R, = 10). Heart histology and the levels of cytokines related to antioxidant and inflammation, as well as protein and mRNA expressions of molecules associated with TGF pathway, were examined in different groups. Our results showed that the reduction of ALK4 expression ameliorated myocardial I/R injury through inhibiting TGF signaling pathway. Our findings indicate that ALK4 may become a novel target for the therapy of myocardial I/R injury.
激活素受体样激酶 4 (ALK4) 信号的激活在心脏压力超负荷中起着关键作用，ALK4 的单倍体缺失可通过部分抑制 Smad3/4 通路减轻心肌梗死后的心肌纤维化并维持心脏功能。然而，ALK4 敲低对缺血性心脏的有益作用是否涉及转化生长因子 (TGF) 信号仍不清楚。本研究旨在探讨 ALK4 敲低后 TGF 信号的变化及其在体外的变化。40 只 C57BL/6J 小鼠随机分为 ALK4 缺血/再灌注 (I/R) 组 (ALK4+I/R, = 10)、ALK4 假手术组 (ALK4+sham, = 10)、野生型假手术组 (WT+sham, = 10) 和 WT I/R 组 (WT+I/R, = 10)。在不同组中检查心脏组织学以及与抗氧化和炎症相关的细胞因子水平，以及与 TGF 通路相关的分子的蛋白和 mRNA 表达。我们的结果表明，ALK4 表达的减少通过抑制 TGF 信号通路改善了心肌 I/R 损伤。我们的研究结果表明，ALK4 可能成为心肌 I/R 损伤治疗的新靶点。
