MicroRNA-30/Cx43 axis contributes to podocyte injury by regulating ER stress in diabetic nephropathy
| العنوان: | MicroRNA-30/Cx43 axis contributes to podocyte injury by regulating ER stress in diabetic nephropathy |
|---|---|
| المؤلفون: | Weijie Ni, Yubo Ma, Weilang Wang, Min Yang, Mengyu Zhang, Xiwei Hong, Xinyang Yu, Min Li, Fei Hua, Mengting Chen, Shusu Liu |
| المصدر: | Ann Transl Med |
| بيانات النشر: | AME Publishing Company, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, TUNEL assay, medicine.diagnostic_test, General Medicine, Transfection, Biology, medicine.disease, Podocyte, Cell biology, Diabetic nephropathy, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, medicine.anatomical_structure, Western blot, 030220 oncology & carcinogenesis, microRNA, cardiovascular system, Unfolded protein response, medicine, Gene silencing, Original Article |
| الوصف: | Background The microRNA-30 family plays a critical role in the pathogenesis of podocyte injury. Cx43 plays an essential role in intercellular communication, which is essential for coordinated kidney function. This study was conducted to explore the function of microRNA-30s/Cx43 in podocyte injury in diabetic nephropathy (DN), both in vivo and in vitro. Methods SD rats were given streptozotocin (STZ) injections to induce DN. Podocytes were incubated in the medium in the presence or absence of high glucose (HG). The effects of the microRNA-30/Cx43 axis on DN and its underlying mechanisms were investigated by TUNEL assay, PAS, immunohistochemical staining, immunofluorescence staining, Western blot, RT-qPCR, RNA interference, and luciferase reporter assay. Podocytes were transfected with microRNA-30 family mimics, microRNA-30 family inhibitors, Cx43 siRNA, and negative controls to detect the effect of the microRNA-30/Cx43 axis. MicroRNA-30 family mimic AAVs, and microRNA-30 family inhibitor AAVs applied to regulate microRNA-30 family expression in the kidneys of the STZ-induced DN model rats to reveal the underlying mechanisms of the microRNA-30/Cx43 axis in DN. Results MicroRNA-30 family member expression was downregulated in HG-treated podocytes and the glomeruli of STZ-induced DN rats. Luciferase reporter assays confirmed Cx43 is a directed target of microRNA-30s. The overexpression of microRNA-30 family members attenuated the HG-induced podocyte injury and protected against podocyte apoptosis and endoplasmic reticulum stress (ERS) both in vivo and in vitro. Also, silencing Cx43 expression eased podocyte apoptosis, injury, and ERS induced by a HG+microRNA-30 family inhibitor. Double-immunofluorescence staining assays proved the co-localization of caspase12 and Cx43. Conclusions The overexpression of microRNA-30 family members prevents HG-induced podocyte injury and attenuates ERS by modulating Cx43 expression. The microRNA-30/Cx43/ERS axis might be a potential therapeutic target to treat DN. |
| تدمد: | 2305-5847 2305-5839 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d52c1db24f68d95824a3df2189094aec https://doi.org/10.21037/atm-20-6989 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....d52c1db24f68d95824a3df2189094aec |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 23055847 23055839 |
|---|