Zinc finger GATA-like protein 1 regulates apoptosis and phenotypic transformation via protein kinase B pathway in human vascular smooth muscle cells.

Abstract

Purpose: Intracranial aneurysms represent the primary source of subarachnoid hemorrhage, ranking as the third most common cerebrovascular disorder after cerebral thrombosis and hypertension-related brain hemorrhage. As a member of the GATA family transcription factors, the role of zinc finger GATA-like protein 1 (ZGLP1) was unclear in intracranial aneurysm. In the present research, the specific effects of ZGLP1 on the proliferation and phenotypic transformation of human aerobic smooth muscle cells (HASMCs) were investigated.

Methods: Cell counting kit 8 and colony formation assays were performed to detect the growth of HASMCs. Cell migration was confirmed using transwell and wound healing assays. The apoptosis was analyzed using flow cytometry.

Finding: ZGLP1 knockdown inhibited the viability and colony formation ability of HASMCs. Importantly, ZGLP1 knockdown effectively promoted the apoptosis of HASMCs. The migration of HASMCs was remarkably inhibited by ZGLP1-specific small interfering RNA. Mechanistically, ZGLP1 knockdown inhibits the phosphorylation of protein kinase B (AKT) and cyclin D1 expression. In addition, ZGLP1 knockdown inhibited the expression of SMA and SM22α, while promoting the expression of OPN and MMP-2 in HASMCs, suggesting that ZGLP1 knockdown initiated the transformation from contractile phenotype to synthetic phenotype of HASMCs.

Conclusion: ZGLP1 knockdown induces apoptosis through the AKT pathway, and also induces the phenotypic transformation of HASMCs. ZGLP1 is a potential therapeutic target for intracranial aneurysm and deserves further research.