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MicroRNA-208-5p regulates myocardial injury of sepsis mice via targeting SOCS2-mediated NF-κB/HIF-1α pathway.

Abstract：

BACKGROUND:Accumulating evidence has revealed the roles of microRNAs (miRs) in sepsis, hence, the aim of the present study was to investigate whether miR-208a-5p affects sepsis whilst attempting to elucidate the mechanisms by which the suppressors of cytokine signaling 2 (SOCS2)-mediated nuclear factor-kappaB/hypoxia-inducible factor-1α (NF-κB/HIF-1α) pathway is implicated in this process. METHODS:The sepsis model was established by cecal ligation and puncture in mice. Serum levels of myocardial enzyme cardiac Troponin-I (cTnI) and brain natriuretic peptide (BNP) in mice were measured. Malondialdehyde (MDA), lactate dehydrogenase (LDH) activity, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), NF-κB p65, HIF-1α and superoxidedismutase (SOD) activity in myocardial tissues were determined. Furthermore, the swelling degree of mitochondria and the apoptosis of cardiomyocytes was measured. The expression of miR-208a-5p, SOCS2, Bcl-2, Bax, NF-κB p65 and HIF-1α in myocardial tissues of mice were detected. RESULTS:Down-regulation of miR-208a-5p and up-regulation of SOCS2 raised the activity of SOD, while reduced the activity of LDH and MDA and the concentrations of cTnI, BNP, TNF-α, IL-6, NF-κB p65 and HIF-1α in mice with sepsis. Down-regulated miR-208a-5p and up-regulated SOCS2 reduced degree of mitochondria swelling, and suppressed cardiomyocytes apoptosis in mice with sepsis. MiR-208a-5p, NF-κB p65 and HIF-1α expression were raised while SOCS2 expression was depressed in myocardial tissues of mice with sepsis. CONCLUSION:This study suggests that high expression of SOCS2 or inhibition of miR-208a-5p alleviates the myocardial injury of sepsis mice via modulating NF-κB/HIF-1α pathway, which are potential candidate markers and therapeutic targets for sepsis mice.

journal_name

Int Immunopharmacol

journal_title

International immunopharmacology

authors

Ouyang H,Tan Y,Li Q,Xia F,Xiao X,Zheng S,Lu J,Zhong J,Hu Y

doi

10.1016/j.intimp.2020.106204

subject

Has Abstract

pub_date

2020-04-01 00:00:00

pages

106204

eissn

1567-5769

issn

1878-1705

pii

S1567-5769(19)31898-3

journal_volume

pub_type

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MicroRNA-208-5p regulates myocardial injury of sepsis mice via targeting SOCS2-mediated NF-κB/HIF-1α pathway.