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 (NK₁R) 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^7daysI/R, LV^7daysSP+I/R) and infarct-related areas (IA; IA^7daysI/R, IA^7daysSP+I/R) from the hearts were collected. Immunofluorescence staining demonstrated that the LV^7daysSP+I/R had a larger population of c-Kit⁺ GATA4^high cells, which markedly upregulated MITF, c-Kit, and GATA4. c-Kit⁺ cells in the explant-derived cells (EDCs) derived from IA^7daysSP+I/R migrated more widely than EDCs IA^7daysI/R. 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 (NK₁R 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.

中文翻译：

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心肌梗塞后施用的P物质上调了与小眼科相关的转录因子，GATA4和c-Kit +细胞的扩增。

小眼症相关转录因子（MITF）是一种基本的螺旋-环-螺旋亮氨酸拉链转录因子，可以通过结合靶基因启动子区域的E盒元件来控制基因表达。尽管在心肌细胞和心脏中观察到高水平的MITF，但心肌梗死（MI）后MITF的作用仍不清楚。我们调查了物质P（SP）/神经激肽-1受体（NK ₁ R）信号传导与MI后MITF表达之间的关联。将雄性Sprague-Dawley大鼠（8周）随机分为两组：缺血/再灌注损伤（I / R）和SP注射（5 nmol / kg，SP + I / R）。在第7天结束时，左心室（LV; LV ^{7daysI / R}，LV ^{7daysSP + I / R}）和梗塞相关区域（IA; IA ^{7daysI / R}，从心脏收集IA ^{7daysSP + I / R}）。免疫荧光染色表明，LV ^{7daysSP + I / R}具有大量c-Kit ⁺ GATA4^高细胞，显着上调了MITF，c-Kit和GATA4。IA ^{7daysSP + I / R}衍生的外植体衍生细胞（EDC）中的c-Kit ⁺细胞比IA ^{7daysI / R的}EDC迁移更广泛。免疫荧光染色，蛋白质印迹分析和qRT-PCR分析表明，经SP处理的c-Kit ⁺细胞表现出高表达的c-Kit，GATA4和MITF。FTY720（一种MITF抑制剂），RP67580（一种NK ₁ R抑制剂）或两者均抑制c-Kit的迁移和增殖SP使⁺细胞增加，并阻止c-Kit，GATA4和MITF的上调。总体而言，我们建议MITF可能是通过c-Kit和GATA4在MI后SP介导的c-Kit ⁺细胞扩增中的潜在调节剂。