Inhibition of miR‑101‑3p protects against sepsis‑induced myocardial injury by inhibiting MAPK and NF‑κB pathway activation via the upregulation of DUSP1

Xin,Ye; Tang,Li; Chen,Jing; Chen,Dong; Wen,Wen; Han,Fugang

doi:10.3892/ijmm.2021.4853

Inhibition of miR‑101‑3p protects against sepsis‑induced myocardial injury by inhibiting MAPK and NF‑κB pathway activation via the upregulation of DUSP1

Authors:
- Ye Xin
- Li Tang
- Jing Chen
- Dong Chen
- Wen Wen
- Fugang Han
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Affiliations: Department of Radiology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, P.R. China, Department of Gastroenterology, Xinqiao Hospital of Army Medical University, Chongqing 400037, P.R. China
Published online on: January 13, 2021 https://doi.org/10.3892/ijmm.2021.4853
Article Number: 20
Copyright: © Xin et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Numerous studies have found that microRNAs (miRNAs or miRs) are aberrantly expressed when sepsis occurs. The present study aimed to investigate the role of miR‑101‑3p in sepsis‑induced myocardial injury and to elucidate the underlying mechanisms. Models of myocardial injury were established both in vivo and in vitro. The results revealed that miR‑101‑3p was upregulated in the serum of patients with sepsis‑induced cardiomyopathy (SIC) and positively correlated with the levels of pro‑inflammatory cytokines (including IL‑1β, IL‑6 and TNF‑α). Subsequently, rats were treated with miR‑101‑3p inhibitor to suppress miR‑101‑3p and were then exposed to lipopolysaccharide (LPS). The results revealed that LPS induced marked cardiac dysfunction, apoptosis and inflammation. The inhibition of miR‑101‑3p markedly attenuated sepsis‑induced myocardial injury by attenuating apoptosis and the expression of pro‑inflammatory cytokines. Mechanistically, dual specificity phosphatase‑1 (DUSP1) was found to be a functional target of miR‑101‑3p. The downregulation of miR‑101‑3p led to the overexpression of DUSP1, and the inactivation of the MAPK p38 and NF‑κB pathways. Moreover, blocking DUSP1 by short hairpin RNA against DUSP1 (sh‑DUSP1) significantly reduced the myocardial protective effects mediated by the inhibition of miR‑101‑3p. Collectively, the findings of the present study demonstrate that the inhibition of miR‑101‑3p exerts cardioprotective effects by suppressing MAPK p38 and NF‑κB pathway activation, and thus attenuating inflammation and apoptosis dependently by enhancing DUSP1 expression.

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