Cardiometabolic Research Group and MTA-SE System Pharmacology Research Group Department of Pharmacology and Pharmacotherapy, Semmelweis University, 1085 Budapest, Hungary.
Pharmahungary Group, H-6720 Szeged, Hungary.
Int J Mol Sci. 2020 May 9;21(9):3359. doi: 10.3390/ijms21093359.
Swiprosin-1 (EFhD2) is a molecule that triggers structural adaptation of isolated adult rat cardiomyocytes to cell culture conditions by initiating a process known as cell spreading. This process mimics central aspects of cardiac remodeling, as it occurs subsequent to myocardial infarction. However, expression of swiprosin-1 in cardiac tissue and its regulation in vivo has not yet been addressed. The expression of swiprosin-1 was analyzed in mice, rat, and pig hearts undergoing myocardial infarction or ischemia/reperfusion with or without cardiac protection by ischemic pre- and postconditioning. In mouse hearts, swiprosin-1 protein expression was increased after 4 and 7 days in myocardial infarct areas specifically in cardiomyocytes as verified by immunoblotting and histology. In rat hearts, swiprosin-1 mRNA expression was induced within 7 days after ischemia/reperfusion but this induction was abrogated by conditioning. As in cultured cardiomyocytes, the expression of swiprosin-1 was associated with a coinduction of arrestin-2, suggesting a common mechanism of regulation. Rno-miR-32-3p and rno-miR-34c-3p were associated with the regulation pattern of both molecules. Moreover, induction of swiprosin-1 and ssc-miR-34c was also confirmed in the infarct zone of pigs. In summary, our data show that up-regulation of swiprosin-1 appears in the postischemic heart during cardiac remodeling and repair in different species.
Swiprosin-1 (EFhD2) 是一种分子,通过启动细胞铺展过程,触发分离的成年大鼠心肌细胞对细胞培养条件的结构适应。这个过程模拟了心肌梗死后心脏重构的核心方面。然而,swiprosin-1 在心脏组织中的表达及其在体内的调节尚未得到解决。我们分析了在经历心肌梗死或缺血/再灌注的小鼠、大鼠和猪心脏中 swiprosin-1 的表达,以及是否存在缺血预处理和后处理的心脏保护。在小鼠心脏中,在心肌梗死区域中,swiprosin-1 蛋白表达在 4 天和 7 天后特异性地在心肌细胞中增加,这通过免疫印迹和组织学得到证实。在大鼠心脏中,在缺血/再灌注后 7 天内诱导了 swiprosin-1 mRNA 表达,但这种诱导被预处理所阻断。与在培养的心肌细胞中一样,swiprosin-1 的表达与 arrestin-2 的共同诱导相关,表明存在共同的调节机制。Rno-miR-32-3p 和 rno-miR-34c-3p 与这两种分子的调节模式相关。此外,在猪的梗死区也证实了 swiprosin-1 和 ssc-miR-34c 的诱导。总之,我们的数据表明,在不同物种的心脏重构和修复过程中,swiprosin-1 的上调出现在缺血后的心脏中。