J Biol Regul Homeost Agents. May-Jun 2021; 35(3):1029-1040. doi: 10.23812/21-201-A.


ORIGINAL ARTICLE


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High dose insulin promotes the proliferation of vascular smooth muscle cells via AP-1/SM-α pathway

Peng Y1, Cai P1, Zou SF2, Jia M1, Zhong WT1, Wang Y3, Wang XK1.

Author information

1  Department of Cardiology, Institute of Field Surgery, Daping Hospital, Army Medical University, Yuzhong District, Chongqing, P.R. China.
2  Department of Cardiac Surgery, Xinqiao Hospital, Army Medical University Shapingba District, Chongqing, P.R. China.
3  Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Honghuagang District, Zunyi, Guizhou, P.R. China.

Abstract

Proliferation of vascular smooth muscle cells (VSMCs) participates in multiple cardiovascular disorders, while the mechanism remains unclear. This study aims to investigate the effects of insulin on VSMC. Insulin was used to stimulate rat VSMCs, and the effects on cell cycle and proliferation were subsequently analyzed using flow cytometry. Furthermore, AP-1 and SM-α overexpression vectors were constructed and transfected into VSMCs. AP-1 and SM-α were inhibited by SR11302 and SM-α siRNA, respectively. The mRNA and protein expression levels were subsequently detected using the reversetranscription quantitative polymerase chain reaction and western blotting, respectively. AP-1 and SM-α gene promoter binding sites were determined using luciferase and chromatin immunoprecipitation assays. As a result, we found that high dose of insulin promoted proliferation of VSMCs and increased the percentage of cells in the S phase by downregulating AP-1. AP-1 was identified to bind to the SM-α gene promoter at locus 2-177 to upregulate SM-α gene expression. Inhibition of AP-1 led to the decrease of SM-α expression. Overexpression of SM-α directly suppressed proliferation of VSMCs, while knocking it down promoted the process. Therefore, this study revealed that insulin downregulated the expression of the SM-α gene by inhibiting AP-1, which in turn facilitated proliferation of VSMCs.

KEYWORDS:

activator protein 1, insulin, proliferation, smooth muscle alpha-actin, vascular smooth muscle cell

Publication type

  • Journal Article

 


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