Inhibition of p38MAPK potentiates mesenchymal stem cell therapy against myocardial infarction injury in rats

Zhang,Zhiling; Zhou,Shulan; Mei,Zhiliang; Zhang,Ming

doi:10.3892/mmr.2017.6973

Inhibition of p38MAPK potentiates mesenchymal stem cell therapy against myocardial infarction injury in rats

Authors:
- Zhiling Zhang
- Shulan Zhou
- Zhiliang Mei
- Ming Zhang
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Affiliations: Medical School of Nanchang University, Nanchang, Jiangxi 330006, P.R. China, The Second Department of Cardiovascular Medicine, Jiangxi Provincial People's Hospital, Nanchang, Jiangxi 330006, P.R. China
Published online on: July 14, 2017 https://doi.org/10.3892/mmr.2017.6973
Pages: 3489-3493

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Abstract

The present study aimed to investigate the protective effect of mesenchymal stem cell (MSC) therapy in combination with p38 mitogen‑activated protein (MAPK) inhibition against myocardial infarction (MI) injury in rats, and to elucidate the underlying mechanisms. An MI model was established by ligation of the anterior descending branch of the left coronary artery. The rats were divided into four groups: MSC transplantation, p38MAPK inhibitor (SB203580), MSC + SB203580 and model control group. HE staining and a TUNEL assay were performed to evaluate pathological changes and apoptosis. The expression levels of p38MAPK and transforming growth factor β‑activated kinase 1 (TAK1) were determined using reverse transcription‑polymerase chain reaction and western blot analyses. As shown by HE staining, classical morphological changes, including irregular cell arrangement and inflammatory infiltration were observed in the model rats, whereas MSC therapy or injection of the p38MAPK inhibitor ameliorated these pathological changes. Of note, the combined application of MSCs with the p38MAPK inhibitor exerted additive effects. The TUNEL assay showed that the combined application of MSCs with p38MAPK inhibitor also led to potentiation of effects, compared with either MSCs therapy or p38MAPK inhibitor injection alone. Mechanistically, the combined application of MSCs with p38MAPK inhibitor decreased the expression levels of TAK1 and p38MAPK at the mRNA and protein levels. In conclusion, p38MAPK inhibition potentiated the protective effects of MSCs therapy against MI in rats.

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