Substance P Administered after Myocardial Infarction Upregulates Microphthalmia-Associated Transcription Factor, GATA4, and the Expansion of c-Kit+ Cells. (10th February 2020)

• Record Type: Journal Article
• Authors: Jeong, Yun-Mi; Cheng, Xian Wu; Kim, Weon
• Other Names: Pisciotta Alessandra Academic Editor.
• Is Part Of: Stem cells international. Volume 2020(2020)
• Publication Date: 2020-02-10
• Subjects: Stem Cells -- Periodicals; Stem Cells -- Therapeutic use -- Periodicals; Stem Cells -- Transplantation -- Periodicals; 616.0277405
• DOI: 10.1155/2020/1835950
• Languages: English
• ISSNs: 1687-966X

Abstract

Abstract : 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 (NK1 R) 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 (NK1 R 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.