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

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.

Collagen Peptide Upregulates Osteoblastogenesis from Bone Marrow Mesenchymal Stem Cells through MAPK- Runx2

“…It was earlier confirmed by few authors that certain specific amino acid domain (asparagine, glycine, glutamine, and alanine) of collagen interact with α 2 β 1 integrin on the bone marrow mesenchymal stem cell membrane and can lead to up-regulate bone matrix synthesis through activation of Runx2 signaling pathway [29,36,41,49,50]. Kawaguchi et al [51] observed the presence of radioactive dipeptides [14C] Pro-Hyp in osteoblasts, osteoclasts, dermal fibroblasts, epidermal cells, synovial cells, and chondrocytes after 24 h of oral administration.…”

The Micro-RNA Cargo of Extracellular Vesicles Released by Human Adipose Tissue-Derived Mesenchymal Stem Cells Is Modified by Obesity

“…Activation of p38 elicits protective effects during ischemic conditions ( Nakano et al, 2000 ; Fujimoto et al, 2004 ; Hsu et al, 2007 ) and plays an important role in the activation of brown adipose tissue ( Leiva et al, 2020 ). However, activation of p38 has been linked to inflammatory cytokine production ( Li et al, 2005 ) and ASC aging ( Zhang et al, 2020 ), and its inhibition potentiates ASC and EV therapy ( Zhang et al, 2017 ; Chen et al, 2020 ). Our in vitro studies revealed that treatment of uninjured HK2 cells with EVs increased expression of p-p38, underscoring the potential of EVs to activate members of MAPK signaling in recipient cells.…”

The therapeutic potential of mesenchymal stem cells for cardiovascular diseases

“…Meanwhile, other reports to improve the complex microenvironment in heart diseases have been published. Myocardial transfection of HIF-1α via an adenoviral vector or injection of p38MAPK inhibitor (SB203580) was used to optimize to effects of transplanted MSCs 76,77 . The impact of heart disease environment on the transplanted MSCs and the approach to improve to transplantation-site microenvironment are worth exploring in the future.…”