Nephroprotective effect of AT-MSCs against cisplatin-induced EMT is improved by azilsartan via attenuating oxidative stress and TGF-β/Smad signaling - 13/01/23
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Abstract |
The nephrotoxicity of cisplatin (CIS) is a significant complication that challenges its clinical applicability. The epithelial to mesenchymal transition (EMT) may be included in the pathogenesis of CIS-evoked nephrotoxicity. Therefore, the current study aimed to evaluate, for the first time, the possible protective effect of AZL and/or AT-MSCs against CIS–induced EMT in rats on molecular bases. Fifty-four healthy Wistar male albino rats were used in this study. Different biochemical markers of kidney function as well as oxidative stress parameters were investigated. Additionally, renal histopathological study was performed. The expression of EMT-related proteins and genes was evaluated by western blotting and qRT-PCR. CIS markedly increased SCr, BUN, uric acid and renal MDA levels, with concomitant decrease in serum total protein, renal GSH level and SOD activity. Furthermore, it suppressed the expression of Cdh1 gene, increased the α-SMA, Acta2, Cdh2 and Vim genes expression, down regulated the expression of E-cad protein and up-regulated the α-SMA, TGF-β1, p-Smad2/3 and Snail proteins expression. Kidney tissues showed severe histopathological alterations and extensive collagen accumulation. Conversely, the treatment with either AZL or AT-MSCs significantly attenuated these alterations caused by CIS. Interestingly, the combined therapy of AZL and AT-MSCs has a superior ameliorative effect than AT-MSCs alone. In conclusion, this study, for the first time, revealed that AZL and/ or AT-MSCs successfully ameliorated the CIS-induced EMT via the inhibition of oxidative stress and TGF-β/Smad signaling pathway. Intriguingly, AZL enhanced the effect of AT-MSCs making them promising agents for kidney protection against CIS-induced EMT.
Le texte complet de cet article est disponible en PDF.Graphical Abstract |
Highlights |
• | CIS induced EMT in kidney. |
• | AZL and/or AT-MSCs showed nephroprotective effects against CIS-induced EMT. |
• | AZL and/or AT-MSCs inhibited oxidative stress signaling pathway. |
• | AZL and/or AT-MSCs inhibited TGF-β/Smad signaling pathway. |
Keywords : Adipose tissue-derived mesenchymal stem cells, Azilsartan, Cisplatin, Nephrotoxicity, Epithelial to mesenchymal transition, TGF-β/Smad, Snail
Plan
Vol 158
Article 114097- février 2023 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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