FoxO1 and Wnt/β-catenin signaling pathway: Molecular targets of human amniotic mesenchymal stem cells-derived conditioned medium (hAMSC-CM) in protection against cerebral ischemia/reperfusion injury

• Published in: Journal of chemical neuroanatomy 2021-03, Vol.112, p.101918-101918, Article 101918
• Main Authors: Nazarinia, Donya, Sharifi, Masoomeh, Dolatshahi, Mojtaba, Nasseri Maleki, Solmaz, Madani Neishaboori, Arian, Aboutaleb, Nahid
• Format: Article
• Language: English
• Subjects: Conditioned medium; FoxO1; Human amniotic mesenchymal stem cells; Ischemic stroke; Wnt/β-catenin signaling pathway
• ISSN: 0891-0618; 1873-6300
• DOI: 10.1016/j.jchemneu.2021.101918

[Display omitted] •hAMSC-conditioned medium is able to suppress inflammation in a rat model of cerebral ischemia/reperfusion injury.•hAMSC-conditioned medium is able to reinforce the endogenous antioxidant system.•Neuroprotective effects of hAMSC-conditioned medium are associated with activation of FoxO1 and Wnt/β-catenin pathway. Ischemia-reperfusion (I/R) injury has weakened the effects of available treatment options for ischemic stroke. Although conditioned medium obtained from human amniotic mesenchymal stem cells (hAMSC-CM) has been reported to exert protective effect against stroke, detailed knowledge about its possible molecular mechanisms is not still completely available. The present study was designed to investigate whether hAMSC-CM can modulate FoxO1 and Wnt/β-catenin signaling pathway after ischemic stroke to create neuroprotective effects. Middle cerebral artery occlusion (MCAO) model with male Wistar rats was used to evaluate the effects of hAMSC-CM on activities of FoxO1, Wnt/β-catenin signaling pathway, and endogenous antioxidant system and apoptotic cell death. The results demonstrated that induction of MCAO significantly reduced activities of FoxO1, Wnt/β-catenin signaling pathway, and endogenous antioxidant system and enhanced apoptotic cell death (P < 0.05). In addition, treatment by hAMSC-CM immediately after cerebral reperfusion resulted in significantly reduced infarct size and increased activities of FoxO1, Wnt/β-catenin signaling pathway, and restoring endogenous antioxidant system and suppressing apoptotic cell death (P < 0.05). Likewise, increased activity of Wnt/β-catenin signaling pathway resulted in suppressing the neuroinflammation by inhibiting the expression of TNF-α and increasing the expression of IL-10. These findings demonstrate that hAMSC-CM can be considered as an excellent candidate in the treatment of acute ischemic stroke in clinical routine.