Mesenchymal stem cell-conditioned medium improved mitochondrial function and alleviated in flammation and apoptosis in non-alcoholic fatty liver disease by regulating SIRT1
Mesenchymal stem cell-conditioned medium improved mitochondrial function and alleviated in flammation and apoptosis in non-alcoholic fatty liver disease by regulating SIRT1
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间充质干细胞条件培养基通过调节 SIRT1 改善非酒精性脂肪性肝病的线粒体功能并减轻炎症和细胞凋亡
DOI：
10.1016/j.bbrc.2021.01.098
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发表时间：
2021
影响因子：
3.1
通讯作者：
Chen Li
中科院分区：
文献类型：
--
作者：
Yang Mengmeng;Cui Yixin;Song Jia;Cui Chen;Wang Lingshu;Liang Kai;Wang Chuan;Sha Sha;He Qin;Hu Huiqing;Guo Xinghong;Zang Nan;Sun Lei;Chen Li
非酒精性脂肪性肝病（NAFLD）是糖尿病的一个新兴危险因素，目前被认为是世界上最常见的肝脏疾病。间充质干细胞（Mesenchymal stem cells, MSCs）在条件培养基（conditional medium， CM）中释放大量分子，是再生医学中一个很有前途的工具。越来越多的证据表明MSC-CM对糖尿病相关NAFLD有益。然而，MSC-CM如何改善NAFLD的机制仍不确定。本研究采用链脲佐菌素（STZ）和高脂饮食（HFD）诱导的T2DM小鼠模型和棕榈酸（PA）刺激的L-O2细胞，研究MSC-CM对NAFLD的影响。我们的研究结果表明，MSC-CM可以改善糖尿病小鼠的胰岛素抵抗，改变肝脏的病理结构，增强肝脏的总抗氧化能力和线粒体功能，减少炎症和细胞凋亡。我们进一步证实SIRT1在介导MSC-CM的保护作用中发挥了关键作用。这些发现为MSC-CM在临床上治疗T2DM合并NAFLD患者提供了新的证据。
Non-alcoholic fatty liver disease (NAFLD), an emerging risk factor for diabetes, is now recognized as the most common liver disease worldwide. Mesenchymal stem cells (MSCs), a promising tool in regenerative medicine, release abundant molecules into the conditioned medium (CM). Increasing evidence showed that MSC-CM is beneficial for diabetes-associated NAFLD. However, the mechanism of how MSC-CM improves NAFLD remains uncertain. In this study, to determine the effects of MSC-CM on NAFLD, streptozotocin (STZ) and high-fat diet (HFD) induced T2DM mice model and palmitic acid (PA)-stimulated L-O2 cells were used and treated with MSC-CM. Our results demonstrated that MSC-CM improved insulin resistance in diabetic mice, amended the pathological structure of the liver, enhanced the liver’s total antioxidant capacity and mitochondrial function, reduced inflammation and cell apoptosis. We further verified that SIRT1 played a key role in mediating the protective effect of MSC-CM. These findings provide novel evidence that MSC-CM has the potential to treat T2DM patients with NAFLD clinically.