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MiR-599 regulates LPS-mediated apoptosis and inflammatory responses through the JAK2/STAT3 signalling pathway via targeting ROCK1 in human umbilical vein endothelial cells.

Abstract：

:MicroRNA plays an integral role in the development of atherosclerosis. Our study aimed to investigate the roles of miR-599 in lipopolysaccharide (LPS)-induced endothelial damage in human umbilical vein endothelial cells (HUVECs). HUVECs were transfected with a miR-599 mimic and negative control, and then exposed to LPS. The expression of miR-599 was detected by quantitative real time-polymerase chain reaction (RT-qPCR). Cell viability was analyzed by CCK-8 assay and trypan blue exclusion assay; the formation of DNA fragments was tested by Cell Death Detection ELISA Plus kit; the incidence of apoptosis was detected by flow cytometry; the expression of p53 and cleaved-caspase 3 (c-caspase 3) was evaluated by western blot. Moreover, the mRNA levels and concentrations of tumour necrosis factor (TNF)-α, interleukin (IL)-6, ICAM-1 and VCAM-1 were assayed by RT-qPCR and ELISA. The results showed that overexpression of miR-599 increased cell viability, reduced DNA fragments, the incidence of apoptosis, as well as the protein levels of p53 and c-caspase 3 in the presence of LPS. TNF-α, IL-6, ICAM-1 and VCAM-1 mRNA levels and concentrations were also decreased upon miR-599 upregulation. In addition, the dual luciferase reporter assay demonstrated that ROCK1 is a direct target of miR-599. MiR-599 overexpression inhibited ROCK1 expression. Induced expression of ROCK1 reversed the roles of miR-599 in apoptosis and inflammation. The gain function of miR-599 function inhibited activation of the JAK2/STAT3 signalling pathway, which was abrogated by overexpression of ROCK1. Taken together, our results indicate that miR-599 attenuates LPS-caused cell apoptosis and inflammatory responses through the JAK2/STAT3 signalling pathway via targeting ROCK1.

journal_name

Clin Exp Pharmacol Physiol

journal_title

Clinical and experimental pharmacology & physiology

authors

Wang J,Du A,Wang H,Li Y

doi

10.1111/1440-1681.13316

subject

Has Abstract

pub_date

2020-08-01 00:00:00

pages

1420-1428

issue

eissn

0305-1870

issn

1440-1681

journal_volume

pub_type

杂志文章

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MiR-599 regulates LPS-mediated apoptosis and inflammatory responses through the JAK2/STAT3 signalling pathway via targeting ROCK1 in human umbilical vein endothelial cells.