miPEP31 inhibits the vascular smooth muscle cell proliferation via cooperation with transcription factor Trps1.

Abstract

Our previous study has found that miPEP31, which is encoded by pri-miRNA-31, inhibits the transcription of pri-miRNA-31 and alleviates angiotensin (Ang) II-induced hypertension. miR-31 is involved in proliferation of primary vascular smooth muscle cells (VSMCs), the key functional cells involved in hypertensive vascular remodeling. However, the role and mechanism of miPEP31 in the proliferation of VSMCs remain unclear. The aim of this study is to investigate whether miPEP31 plays an important role in VSMC proliferation and contributes to vascular remodeling. We found that the administration of synthetic miPEP31 mitigated but miPEP31 deficiency aggravated the Ang II-induced aortic thickness of intima plus media and fibrotic area. miPEP31 is endogenously expressed and penetrates into nuclei in VSMCs. miPEP31 inhibits PDGF-BB-induced VSMC proliferation in a dose-dependent manner and decreases the Ang Ⅱ-induced aortic α-SMA staining area. Mechanistically, we demonstrated that miPEP31 acts as a transcriptional repressor and inhibits miR-31 expression by cooperating with Trps1, a GATA family zinc finger transcription factor. In summary, our study suggests that miPEP31 protects against vascular remodeling in Ang II-infused mice via cooperation with transcription factor Trps1 to inhibit miR-31 expression and, subsequently, VSMC proliferation. This finding highlights the therapeutic effect and role of miPEP31 on hypertensive target organs and functional cells.