Mesenchymal stem cell-derived exosomes exert ameliorative effects in type 2 diabetes by improving hepatic glucose and lipid metabolism via enhancing autophagy
Abstract Background Mesenchymal stem cell (MSC)-based therapy is currently considered to be an effective treatment strategy for diabetes and hepatic disorders, such as liver cirrhosis and non-alcoholic fatty liver disease. Exosomes are important mediators of cellular connections, and increasing evid...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2020-06-01
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| Series: | Stem Cell Research & Therapy |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13287-020-01731-6 |
| _version_ | 1818504299060133888 |
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| author | Qin He Lingshu Wang Ruxing Zhao Fei Yan Sha Sha Chen Cui Jia Song Huiqing Hu Xinghong Guo Mengmeng Yang Yixin Cui Yujing Sun Zheng Sun Fuqiang Liu Ming Dong Xinguo Hou Li Chen |
| author_facet | Qin He Lingshu Wang Ruxing Zhao Fei Yan Sha Sha Chen Cui Jia Song Huiqing Hu Xinghong Guo Mengmeng Yang Yixin Cui Yujing Sun Zheng Sun Fuqiang Liu Ming Dong Xinguo Hou Li Chen |
| author_sort | Qin He |
| collection | DOAJ |
| description | Abstract Background Mesenchymal stem cell (MSC)-based therapy is currently considered to be an effective treatment strategy for diabetes and hepatic disorders, such as liver cirrhosis and non-alcoholic fatty liver disease. Exosomes are important mediators of cellular connections, and increasing evidence has suggested that exosomes derived from MSCs may be used as direct therapeutic agents; their mechanisms of action, however, remain largely unclear. Here, we evaluated the efficacy and molecular mechanisms of human umbilical cord MSC-derived exosomes (HucMDEs) on hepatic glucose and lipid metabolism in type 2 diabetes mellitus (T2DM). Methods HucMDEs were used to treat T2DM rats, as well as palmitic acid (PA)-treated L-O2 cells, in order to determine the effects of HucMDEs on hepatic glucose and lipid metabolism. To evaluate the changes in autophagy and potential signaling pathways, autophagy-related proteins (BECN1, microtubule-associated protein 1 light chain 3 beta [MAP 1LC3B]), autophagy-related genes (ATGs, ATG5, and ATG7), AMP-activated protein kinase (AMPK), and phosphorylated AMPK (p-AMPK) were assessed by Western blotting. Results HucMDEs promoted hepatic glycolysis, glycogen storage, and lipolysis, and reduced gluconeogenesis. Additionally, autophagy potentially contributed to the effects of HucMDE treatment. Transmission electron microscopy revealed an increased formation of autophagosomes in HucMDE-treated groups, and the autophagy marker proteins, BECN1 and MAP 1LC3B, were also increased. Moreover, autophagy inhibitor 3-methyladenine significantly reduced the effects of HucMDEs on glucose and lipid metabolism in T2DM rats. Based on its phosphorylation status, we found that the AMPK signaling pathway was activated and induced autophagy in T2DM rats and PA-treated L-O2 cells. Meanwhile, the transfection of AMPK siRNA or application of the AMPK inhibitor, Comp C, weakened the therapeutic effects of HucMDEs on glucose and lipid metabolism. Conclusions These findings demonstrate that HucMDEs improved hepatic glucose and lipid metabolism in T2DM rats by activating autophagy via the AMPK pathway, which provides novel evidence suggesting the potential for HucMDEs in clinically treating T2DM patients. |
| first_indexed | 2024-12-10T21:35:19Z |
| format | Article |
| id | doaj.art-94ac5c55966e4babbfb62b26dd992639 |
| institution | Directory Open Access Journal |
| issn | 1757-6512 |
| language | English |
| last_indexed | 2024-12-10T21:35:19Z |
| publishDate | 2020-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Stem Cell Research & Therapy |
| spelling | doaj.art-94ac5c55966e4babbfb62b26dd9926392022-12-22T01:32:40ZengBMCStem Cell Research & Therapy1757-65122020-06-0111111410.1186/s13287-020-01731-6Mesenchymal stem cell-derived exosomes exert ameliorative effects in type 2 diabetes by improving hepatic glucose and lipid metabolism via enhancing autophagyQin He0Lingshu Wang1Ruxing Zhao2Fei Yan3Sha Sha4Chen Cui5Jia Song6Huiqing Hu7Xinghong Guo8Mengmeng Yang9Yixin Cui10Yujing Sun11Zheng Sun12Fuqiang Liu13Ming Dong14Xinguo Hou15Li Chen16Department of Endocrinology, Qilu Hospital of Shandong UniversityDepartment of Endocrinology, Qilu Hospital of Shandong UniversityDepartment of Endocrinology, Qilu Hospital of Shandong UniversityDepartment of Endocrinology, Qilu Hospital of Shandong UniversityDepartment of Endocrinology, Qilu Hospital of Shandong UniversityDepartment of Endocrinology, Qilu Hospital of Shandong UniversityDepartment of Endocrinology, Qilu Hospital of Shandong UniversityDepartment of Endocrinology, Qilu Hospital of Shandong UniversityDepartment of Endocrinology, Qilu Hospital of Shandong UniversityDepartment of Endocrinology, Qilu Hospital of Shandong UniversityDepartment of Endocrinology, Qilu Hospital of Shandong UniversityDepartment of Endocrinology, Qilu Hospital of Shandong UniversityDepartment of Endocrinology, Qilu Hospital of Shandong UniversityDepartment of Endocrinology, Qilu Hospital of Shandong UniversityDepartment of Endocrinology, Qilu Hospital of Shandong UniversityDepartment of Endocrinology, Qilu Hospital of Shandong UniversityDepartment of Endocrinology, Qilu Hospital of Shandong UniversityAbstract Background Mesenchymal stem cell (MSC)-based therapy is currently considered to be an effective treatment strategy for diabetes and hepatic disorders, such as liver cirrhosis and non-alcoholic fatty liver disease. Exosomes are important mediators of cellular connections, and increasing evidence has suggested that exosomes derived from MSCs may be used as direct therapeutic agents; their mechanisms of action, however, remain largely unclear. Here, we evaluated the efficacy and molecular mechanisms of human umbilical cord MSC-derived exosomes (HucMDEs) on hepatic glucose and lipid metabolism in type 2 diabetes mellitus (T2DM). Methods HucMDEs were used to treat T2DM rats, as well as palmitic acid (PA)-treated L-O2 cells, in order to determine the effects of HucMDEs on hepatic glucose and lipid metabolism. To evaluate the changes in autophagy and potential signaling pathways, autophagy-related proteins (BECN1, microtubule-associated protein 1 light chain 3 beta [MAP 1LC3B]), autophagy-related genes (ATGs, ATG5, and ATG7), AMP-activated protein kinase (AMPK), and phosphorylated AMPK (p-AMPK) were assessed by Western blotting. Results HucMDEs promoted hepatic glycolysis, glycogen storage, and lipolysis, and reduced gluconeogenesis. Additionally, autophagy potentially contributed to the effects of HucMDE treatment. Transmission electron microscopy revealed an increased formation of autophagosomes in HucMDE-treated groups, and the autophagy marker proteins, BECN1 and MAP 1LC3B, were also increased. Moreover, autophagy inhibitor 3-methyladenine significantly reduced the effects of HucMDEs on glucose and lipid metabolism in T2DM rats. Based on its phosphorylation status, we found that the AMPK signaling pathway was activated and induced autophagy in T2DM rats and PA-treated L-O2 cells. Meanwhile, the transfection of AMPK siRNA or application of the AMPK inhibitor, Comp C, weakened the therapeutic effects of HucMDEs on glucose and lipid metabolism. Conclusions These findings demonstrate that HucMDEs improved hepatic glucose and lipid metabolism in T2DM rats by activating autophagy via the AMPK pathway, which provides novel evidence suggesting the potential for HucMDEs in clinically treating T2DM patients.http://link.springer.com/article/10.1186/s13287-020-01731-6ExosomeMesenchymal stem cellGlucose metabolismType 2 diabetes mellitusAutophagy |
| spellingShingle | Qin He Lingshu Wang Ruxing Zhao Fei Yan Sha Sha Chen Cui Jia Song Huiqing Hu Xinghong Guo Mengmeng Yang Yixin Cui Yujing Sun Zheng Sun Fuqiang Liu Ming Dong Xinguo Hou Li Chen Mesenchymal stem cell-derived exosomes exert ameliorative effects in type 2 diabetes by improving hepatic glucose and lipid metabolism via enhancing autophagy Stem Cell Research & Therapy Exosome Mesenchymal stem cell Glucose metabolism Type 2 diabetes mellitus Autophagy |
| title | Mesenchymal stem cell-derived exosomes exert ameliorative effects in type 2 diabetes by improving hepatic glucose and lipid metabolism via enhancing autophagy |
| title_full | Mesenchymal stem cell-derived exosomes exert ameliorative effects in type 2 diabetes by improving hepatic glucose and lipid metabolism via enhancing autophagy |
| title_fullStr | Mesenchymal stem cell-derived exosomes exert ameliorative effects in type 2 diabetes by improving hepatic glucose and lipid metabolism via enhancing autophagy |
| title_full_unstemmed | Mesenchymal stem cell-derived exosomes exert ameliorative effects in type 2 diabetes by improving hepatic glucose and lipid metabolism via enhancing autophagy |
| title_short | Mesenchymal stem cell-derived exosomes exert ameliorative effects in type 2 diabetes by improving hepatic glucose and lipid metabolism via enhancing autophagy |
| title_sort | mesenchymal stem cell derived exosomes exert ameliorative effects in type 2 diabetes by improving hepatic glucose and lipid metabolism via enhancing autophagy |
| topic | Exosome Mesenchymal stem cell Glucose metabolism Type 2 diabetes mellitus Autophagy |
| url | http://link.springer.com/article/10.1186/s13287-020-01731-6 |
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