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Antioxidant Sirt1/Akt axis expression in resveratrol pretreated adipose‐derived stem cells increases regenerative capability in a rat model with cardiomyopathy induced by diabetes mellitus
Journal of Cellular Physiology ( IF 4.5 ) Pub Date : 2021-01-09 , DOI: 10.1002/jcp.30057
Tung‐Sheng Chen, Shou‐Ying Chuang, Chia‐Yao Shen, Tsung‐Jung Ho, Ruey‐Lin Chang, Yu‐Lan Yeh, Chia‐Hua Kuo, B. Mahalakshmi, Wei‐Wen Kuo, Chih‐Yang Huang

High‐glucose (HG) suppresses mesenchymal stem cell (MSC) functions, resulting in a decrease in cardiac regenerative capability for MSC in diabetes mellitus (DM). Resveratrol enhances MSC functions under stress. This study explores if cardiac regenerative capability can be enhanced in MSCs pretreated with resveratrol in DM rats receiving MSCs. In vitro evidence confirms that HG decreases MSCs capability through suppression of survival markers, AMP‐activated protein kinase (AMPK)/Sirtuin 1 (Sirt1) axis, and expression of apoptotic markers. All of these markers are improved when MSCs are cocultured with resveratrol. Wistar male rats were randomly divided into Sham, DM (DM rats), DM rats with autologous transplantation of adipose‐derived stem cells (DM + ADSC), and DM rats with resveratrol pretreated ADSC (DM + RSVL‐ADSC). Compared to the Sham, DM induces pathological pathways (including fibrosis, hypertrophy, and apoptosis) and suppresses survival as well as the AMPK/Sirt1 axis in the DM group. DM + ADSC slightly improves the above pathways whereas DM + RSVL‐ADSC significantly improves the above pathways when compared to the DM group. These results illustrate that resveratrol pretreated with MSCs may show clinical potential in the treatment of heart failure in patients with DM.

中文翻译:


白藜芦醇预处理的脂肪干细胞中抗氧化 Sirt1/Akt 轴的表达可增加糖尿病诱发的心肌病大鼠模型的再生能力



高血糖 (HG) 抑制间充质干细胞 (MSC) 功能,导致糖尿病 (DM) 中 MSC 的心脏再生能力下降。白藜芦醇可增强 MSC 在压力下的功能。本研究探讨了接受白藜芦醇预处理的接受 MSC 的 DM 大鼠中,MSC 的心脏再生能力是否可以增强。体外证据证实,HG 通过抑制生存标记、AMP 激活蛋白激酶 (AMPK)/Sirtuin 1 (Sirt1) 轴和凋亡标记的表达来降低 MSC 的能力。当间充质干细胞与白藜芦醇共培养时,所有这些标记物都会得到改善。 Wistar雄性大鼠随机分为Sham组、DM组(DM大鼠)、自体脂肪干细胞移植DM大鼠(DM+ADSC)、白藜芦醇预处理ADSC组DM大鼠(DM+RSVL-ADSC)。与 Sham 组相比,DM 组诱导病理途径(包括纤维化、肥大和细胞凋亡)并抑制生存以及 AMPK/Sirt1 轴。与 DM 组相比,DM + ADSC 略微改善了上述途径,而 DM + RSVL-ADSC 显着改善了上述途径。这些结果表明,用 MSC 预处理的白藜芦醇可能在治疗 DM 患者心力衰竭方面显示出临床潜力。
更新日期:2021-01-09
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