The Action and Mechanism of Action of MicroRNA-128-3p on Vascular Smooth Muscle Cell Proliferation in Spontaneous Hypertension: An Animal Study

Jing Su, Qing Zhong, Jijin Qi, Xue Yang

Article ID: 7060
Vol 37, Issue 1, 2023
DOI: https://doi.org/10.23812/j.biol.regul.homeost.agents.20233701.12
Received: 8 February 2023; Accepted: 8 February 2023; Available online: 8 February 2023; Issue release: 8 February 2023

Abstract

Background: Essential hypertension as a refractory disease that is considered a major health problem. Proliferation of vascular smooth muscle cell (VSMC) is a key pathological aspect of hypertension. MicroRNAs are small noncoding RNA that modulate gene expression via binding different target genes. The aim of this study was to investigate whether certain miRNAs affect vascular remodeling in hypertension and explore the mechanism of their effect. Methods: We conducted experiments using Wistar-Kyoto rats and Spontaneous Hypertension Rat. Cell-counting-kit-8 and 5-ethynyl-2’-deoxyuridine assays were used to detect cell viability and proliferation. Gene and protein expression were measured using quantitative real time polymerase chain reaction and western blot. Additionally, the target binding was confirmed through luciferase reporter assay. Hematoxylin-eosin staining was used to assess vascular remodeling. Results: The expression levels of miR-128-3p were significantly reduced in Spontaneous Hypertension Rat aorta and vascular smooth muscle cells compared with Wistar-Kyoto. Overexpression of miR-128-3p arrested the function of proliferation in the VSMCs. Kruppel like factor 4 was shown to represent a candidate gene for miR-128-3p, and knockdown of kruppel like factor 4 significantly suppressed the proliferation. Upregulation of miR-128-3p in Spontaneous Hypertension Rat was shown to attenuate vascular remodeling and hypertension. Conclusions: miR-128-3p inhibited Spontaneous Hypertension Rat-vascular smooth muscle cells via targeting kruppel like factor 4.


Keywords

miR-128-3p;kruppel like factor 4;cell proliferation;vascular remodeling


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