Metformin Modulates T Cell Function and Alleviates Liver Injury Through Bioenergetic Regulation in Viral Hepatitis
| العنوان: | Metformin Modulates T Cell Function and Alleviates Liver Injury Through Bioenergetic Regulation in Viral Hepatitis |
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| المؤلفون: | Lanman Xu, Xiaofang Wang, Yan Chen, Lynn Soong, Yongping Chen, Jiyang Cai, Yuejin Liang, Jiaren Sun |
| المصدر: | Frontiers in Immunology, Vol 12 (2021) Frontiers in Immunology |
| بيانات النشر: | Frontiers Media S.A., 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | 0301 basic medicine, FIS1, endocrine system diseases, T cell, Adenoviridae Infections, Immunology, Aspartate transaminase, viral hepatitis, mTORC1, Pharmacology, Mechanistic Target of Rapamycin Complex 1, Lymphocyte Activation, Tuberous Sclerosis Complex 1 Protein, Adenoviridae, 03 medical and health sciences, Mice, 0302 clinical medicine, medicine, Immunology and Allergy, Animals, Humans, Hypoglycemic Agents, Cells, Cultured, Original Research, biology, Chemistry, nutritional and metabolic diseases, RC581-607, medicine.disease, Metformin, Mice, Inbred C57BL, mitochondria, Disease Models, Animal, 030104 developmental biology, medicine.anatomical_structure, Alanine transaminase, Liver, 030220 oncology & carcinogenesis, Hepatitis, Viral, Animal, biology.protein, mTOR, Mitochondrial fission, Female, Immunologic diseases. Allergy, Viral hepatitis, Energy Metabolism, metformin, medicine.drug |
| الوصف: | Metformin is not only the first-line medication for the treatment of type 2 diabetes, but it is also effective as an anti-inflammatory, anti-oxidative and anti-tumor agent. However, the effect of metformin during viral hepatitis remains elusive. Using an adenovirus (Ad)-induced viral hepatitis mouse model, we found that metformin treatment significantly attenuated liver injury, with reduced serum aspartate transaminase (AST) and alanine transaminase (ALT) levels and liver histological changes, presumably via decreased effector T cell responses. We then demonstrated that metformin reduced mTORC1 activity in T cells from infected mice, as evidenced by decreased phosphorylation of ribosome protein S6 (p-S6). The inhibitory effects on the mTORC1 signaling by metformin was dependent on the tuberous sclerosis complex 1 (TSC1). Mechanistically, metformin treatment modulated the phosphorylation of dynamin-related protein 1 (Drp-1) and mitochondrial fission 1 protein (FIS1), resulting in increased mass in effector T cells. Moreover, metformin treatment promoted mitochondrial superoxide production, which can inhibit excessive T cell activation in viral hepatitis. Together, our results revealed a protective role and therapeutic potential of metformin against liver injury in acute viral hepatitis via modulating effector T cell activation via regulating the mTORC1 pathway and mitochondrial functions. |
| اللغة: | English |
| تدمد: | 1664-3224 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e9f2d3e62191f0eb24ebf2cb6d10eb8fTest https://www.frontiersin.org/articles/10.3389/fimmu.2021.638575/fullTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....e9f2d3e62191f0eb24ebf2cb6d10eb8f |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 16643224 |
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