Jeong Yun-Mi, Cheng Xian Wu, Kim Weon
Division of Cardiology, Department of Internal Medicine, Kyung Hee University Hospital, Kyung Hee University, Seoul, Republic of Korea.
Department of Mechanical Engineering, Korea Polytechnic University, 237 Sangidaehak Street, Si-heung City, Republic of Korea.
Stem Cells Int. 2020 Feb 10;2020:1835950. doi: 10.1155/2020/1835950. eCollection 2020.
Microphthalmia-associated transcription factor (MITF), a basic helix-loop-helix leucine zipper transcription factor, can govern gene expression by binding to E box elements in the promoter region of its target gene. Although high levels of MITF have been observed in cardiomyocytes and the heart, the role of MITF after myocardial infarction (MI) remains unclear. We investigated the association between substance P (SP)/neurokinin-1 receptor (NKR) signaling and MITF expression after MI. Male Sprague-Dawley rats (8 weeks) were randomly divided in two groups: ischemia/reperfusion injury (I/R) and SP injection (5 nmol/kg, SP+I/R). At the end of 7 days, the left ventricle (LV; LV, LV) and infarct-related areas (IA; IA, IA) from the hearts were collected. Immunofluorescence staining demonstrated that the LV had a larger population of c-Kit GATA4 cells, which markedly upregulated MITF, c-Kit, and GATA4. c-Kit cells in the explant-derived cells (EDCs) derived from IA migrated more widely than EDCs IA. Immunofluorescence staining, western blot analysis, and qRT-PCR assay showed that SP-treated c-Kit cells exhibited a high expression of c-Kit, GATA4, and MITF. FTY720 (a MITF inhibitor), RP67580 (NKR inhibitor), or both inhibited the migration and proliferation of c-Kit cells increased by SP and blocked the upregulation of c-Kit, GATA4, and MITF. Overall, we suggest that MITF might be a potential regulator in SP-mediated c-Kit cell expansion post-MI via c-Kit and GATA4.
小眼畸形相关转录因子（MITF）是一种碱性螺旋-环-螺旋亮氨酸拉链转录因子，可通过与靶基因启动子区域的E盒元件结合来调控基因表达。尽管在心肌细胞和心脏中已观察到高水平的MITF，但心肌梗死（MI）后MITF的作用仍不清楚。我们研究了MI后P物质（SP）/神经激肽-1受体（NKR）信号传导与MITF表达之间的关联。将雄性Sprague-Dawley大鼠（8周龄）随机分为两组：缺血/再灌注损伤（I/R）组和SP注射组（5 nmol/kg，SP+I/R）。在第7天结束时，收集心脏的左心室（LV；LV，LV）和梗死相关区域（IA；IA，IA）。免疫荧光染色显示，LV中有更多的c-Kit GATA4细胞，其显著上调了MITF、c-Kit和GATA4。来自IA的外植体衍生细胞（EDC）中的c-Kit细胞比EDC IA迁移得更广泛。免疫荧光染色、蛋白质印迹分析和qRT-PCR检测表明，SP处理的c-Kit细胞表现出c-Kit、GATA4和MITF的高表达。FTY720（一种MITF抑制剂）、RP67580（NKR抑制剂）或两者均抑制了SP诱导的c-Kit细胞的迁移和增殖，并阻断了c-Kit、GATA4和MITF的上调。总体而言，我们认为MITF可能是MI后SP介导的c-Kit细胞通过c-Kit和GATA4扩增的潜在调节因子。
