Agmatine Induces Apoptosis of MSCs Through the AMPK Pathway
YAO Mengwei1, REN Tingting1,2, HE Xiao1, CHEN Zhuo1, YANG Yi1, XING Wei1, GUO Wei1, AO Luoquan1, LI Zhan1, LIANG Huaping1, XU Xiang1*
Mesenchymal stem cells (MSCs) are widely used in the treatment of injury and immune-related diseases because of their strong capacities of tissue regeneration and immunomodulation. However, the clinical efficacy of MSCs transplantation is limited by cell apoptosis and the mechanism is still unclear. It has been reported that agmatine (AGM) plays a protective role in septic mice through its anti-inflammatory function which inhibiting the production of nitric oxide (NO). Besides, MSCs transplantation is also an effective treatment for sepsis. However, whether AGM affects the survival of MSCs has not been reported, this study aims to investigate the effects of AGM on the survival of MSCs and its molecular mechanisms. Cell surface markers (CD29, CD34, CD44, CD45,CD90, CD105) and three lines of differentiation (adipogenic, osteogenesis and cartilage) had been identified before research. After treatment with AGM, MSCs’ apoptosis and apoptosis-related signaling pathway markers were measured by flow cytometry and Western blot. It was found that AGM induced apoptosis of MSCs through AMPactivated protein kinase (AMPK) activation and mTOR signaling pathway inhibition in a dose-dependent manner which resulting in the up-regulation of apoptosis-related protein expression. However, AMPK siRNA treatment could significantly inhibit the AGM-induced apoptosis of MSCs through reversing mTOR inhibition, AMPK activation and decreasing the expression of apoptosis-related proteins. Our results demonstrated that AGM can induces MSCs apoptosis through the AMPK pathway.
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