Rapamycin Improves Adipose-Derived Mesenchymal Stem Cells (ADMSCs) Renoprotective Effect against Cisplatin-Induced Acute Nephrotoxicity in Rats by Inhibiting the mTOR/AKT Signaling Pathway
Rattachement africain : Égypte, sa. Niveau de preuve : code pays fourni par la source.
Le résumé fourni par la source
Objective: Because the poor survival of transplanted cells in a hostile microenvironment limits stem cell therapy, in the current study, we investigated the effect of rapamycin (Rapa)-preactivated autophagy on the survival and homing of transplanted adipose mesenchymal stem cells (ADMSCs) in a rat model of cisplatin (Cis)-induced nephrotoxicity, as well as the possible role of the mTOR/AKT signaling pathway. Materials and methods: In vitro, ADMSCs isolated from rats were treated with 50 nmol/L rapamycin for 2 h, after which the cytoprotective and autophagy-inducing effects of Rapa were investigated. The cis-induced acute nephrotoxicity rat model was constructed in vivo. ADMSCs and Rapa-ADMSCs were administered into the tail vein before Cis therapy. At 3, 7, and 10 days after Cis injection, all animals were euthanized. The renal functions and morphology as well as autophagy response were assessed. Results: The pretreatment of cultured ADMSCs with Rapa caused a significant increase in autophagic activities and lysosome production of the cells, with a significant increase in the secretion of SDF-1, IL-10 and autophagy promoter LC3 and Beclin from these cells, while mTOR/AKT pathways were inhibited. In addition, the transplantation of Rapa-pretreated ADMSCs restored the kidney functions and morphology dramatically. Renal expression of SDF-1 and HIF1 was upregulated, while expression of IL-6, NF-kB and TGF-β1 was downregulated. Conclusions: We concluded that the preactivation of autophagy with Rapa improves the survival and differentiation of the transplanted ADMSCs by inhibiting the mTOR/AKT signaling pathway, which in turn could significantly attenuate the Cis-induced acute renal injury.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Rapamycin Improves Adipose-Derived Mesenchymal Stem Cells (ADMSCs) Renoprotective Effect against Cisplatin-Induced Acute Nephrotoxicity in Rats by Inhibiting the mTOR/AKT Signaling Pathway
- Date Crossref
- 31/05/2022
- Éditeur
- MDPI AG
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Mansoura University Urology and Nephrology Center Mansoura University, Égypte (code pays fourni par la source)Université ou école supérieure
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Alfaisal University pays non établi dans la noticeUniversité ou école supérieure
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Almaarefa University pays non établi dans la noticeUniversité ou école supérieure
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Faculty of Medicine Medical Physiology Department Mansoura University, Égypte (pays nommé en fin d’affiliation)Université ou école supérieure
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Faculty of Pharmacy Department of Biochemistry Mansoura University, Égypte (pays nommé en fin d’affiliation)Université ou école supérieure
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Faculty of Sciences Chemistry Department Mansoura University, Égypte (pays nommé en fin d’affiliation)Université ou école supérieure
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College of Medicine Department of Basic Medical Sciences pays non établi dans la noticeUniversité ou école supérieure
Urology and Nephrology Center — Mansoura University (Mansoura University, Égypte), Alfaisal University et Almaarefa University, avec 4 autres affiliations. Pays d’affiliation : Égypte.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.