Tacrolimus Protects Podocytes from Apoptosis via Downregulation of TRPC6 in Diabetic Nephropathy
Podocyte injury plays an important role in diabetic nephropathy (DN), and apoptosis is one of its mechanisms. The transient receptor potential channel 6 (TRPC6) is expressed in podocytes and mediates podocyte injury induced by high glucose levels. Tacrolimus is a novel immunosuppressive agent that i...
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| Format: | Article |
| Language: | English |
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Wiley
2021-01-01
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| Series: | Journal of Diabetes Research |
| Online Access: | http://dx.doi.org/10.1155/2021/8832114 |
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| author | Ruixia Ma Ying Wang Yan Xu Rui Wang Xianghua Wang Ning Yu Minghui Li Yan Zhou |
| author_facet | Ruixia Ma Ying Wang Yan Xu Rui Wang Xianghua Wang Ning Yu Minghui Li Yan Zhou |
| author_sort | Ruixia Ma |
| collection | DOAJ |
| description | Podocyte injury plays an important role in diabetic nephropathy (DN), and apoptosis is one of its mechanisms. The transient receptor potential channel 6 (TRPC6) is expressed in podocytes and mediates podocyte injury induced by high glucose levels. Tacrolimus is a novel immunosuppressive agent that is reported to play an important role in podocyte protection. The purpose of this study was to investigate the potential mechanism of podocyte protection by tacrolimus in a type 2 diabetic mellitus (T2DM) rat model and in immortalized mouse podocytes (MPC5). Transmission electron microcopy was used to evaluate renal injury morphology. After treatment with FK506, we measured 24-hour urinary albumin-to-creatinine ratios and creatinine clearance rates as well as major biochemical parameters such as glucose, insulin, serum creatinine, urea nitrogen, total cholesterol, triglycerides, alanine transaminase, and aspartate aminotransferase. Nephrin and TRPC6 protein expression and podocyte apoptotic rates in vivo and in vitro were measured using immunohistochemical staining, TUNEL assays, and flow cytometry, respectively. Western blot was used to measure expression of cleaved-caspase-3 and bax/bcl-2. Exposed to high glucose (HG), DM rats exhibited disrupted biochemical conditions and impaired podocyte structure. Decreased expression of nephrin and increased expression of TRPC6, cleaved-caspase-3, and bax/bcl-2 ratios were found in podocytes, along with higher apoptotic percentage, while tacrolimus intervention counteracted the effect of HG on podocytes. Our results suggest that tacrolimus protects podocytes during the progression of type 2 diabetic nephropathy, possibly ameliorating podocyte apoptosis by downregulating the expression of TRPC6. |
| format | Article |
| id | doaj-art-04accbeb2ddf46f4907702ee52defd23 |
| institution | Kabale University |
| issn | 2314-6745 2314-6753 |
| language | English |
| publishDate | 2021-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Diabetes Research |
| spelling | doaj-art-04accbeb2ddf46f4907702ee52defd232025-02-03T06:07:16ZengWileyJournal of Diabetes Research2314-67452314-67532021-01-01202110.1155/2021/88321148832114Tacrolimus Protects Podocytes from Apoptosis via Downregulation of TRPC6 in Diabetic NephropathyRuixia Ma0Ying Wang1Yan Xu2Rui Wang3Xianghua Wang4Ning Yu5Minghui Li6Yan Zhou7Department of Nephrology, Affiliated Hospital of Qingdao University, Qingdao, Shandong, ChinaDepartment of Nephrology, Affiliated Hospital of Qingdao University, Qingdao, Shandong, ChinaDepartment of Nephrology, Affiliated Hospital of Qingdao University, Qingdao, Shandong, ChinaDepartment of Intensive Care Unit, Affiliated Hospital of Qingdao University, Qingdao, Shandong, ChinaDepartment of Nephrology, Affiliated Hospital of Qingdao University, Qingdao, Shandong, ChinaDepartment of Ultrasound, Affiliated Hospital of Qingdao University, Qingdao, Shandong, ChinaDepartment of Emergency, Affiliated Hospital of Qingdao University, Qingdao, Shandong, ChinaDepartment of Nephrology, Affiliated Hospital of Qingdao University, Qingdao, Shandong, ChinaPodocyte injury plays an important role in diabetic nephropathy (DN), and apoptosis is one of its mechanisms. The transient receptor potential channel 6 (TRPC6) is expressed in podocytes and mediates podocyte injury induced by high glucose levels. Tacrolimus is a novel immunosuppressive agent that is reported to play an important role in podocyte protection. The purpose of this study was to investigate the potential mechanism of podocyte protection by tacrolimus in a type 2 diabetic mellitus (T2DM) rat model and in immortalized mouse podocytes (MPC5). Transmission electron microcopy was used to evaluate renal injury morphology. After treatment with FK506, we measured 24-hour urinary albumin-to-creatinine ratios and creatinine clearance rates as well as major biochemical parameters such as glucose, insulin, serum creatinine, urea nitrogen, total cholesterol, triglycerides, alanine transaminase, and aspartate aminotransferase. Nephrin and TRPC6 protein expression and podocyte apoptotic rates in vivo and in vitro were measured using immunohistochemical staining, TUNEL assays, and flow cytometry, respectively. Western blot was used to measure expression of cleaved-caspase-3 and bax/bcl-2. Exposed to high glucose (HG), DM rats exhibited disrupted biochemical conditions and impaired podocyte structure. Decreased expression of nephrin and increased expression of TRPC6, cleaved-caspase-3, and bax/bcl-2 ratios were found in podocytes, along with higher apoptotic percentage, while tacrolimus intervention counteracted the effect of HG on podocytes. Our results suggest that tacrolimus protects podocytes during the progression of type 2 diabetic nephropathy, possibly ameliorating podocyte apoptosis by downregulating the expression of TRPC6.http://dx.doi.org/10.1155/2021/8832114 |
| spellingShingle | Ruixia Ma Ying Wang Yan Xu Rui Wang Xianghua Wang Ning Yu Minghui Li Yan Zhou Tacrolimus Protects Podocytes from Apoptosis via Downregulation of TRPC6 in Diabetic Nephropathy Journal of Diabetes Research |
| title | Tacrolimus Protects Podocytes from Apoptosis via Downregulation of TRPC6 in Diabetic Nephropathy |
| title_full | Tacrolimus Protects Podocytes from Apoptosis via Downregulation of TRPC6 in Diabetic Nephropathy |
| title_fullStr | Tacrolimus Protects Podocytes from Apoptosis via Downregulation of TRPC6 in Diabetic Nephropathy |
| title_full_unstemmed | Tacrolimus Protects Podocytes from Apoptosis via Downregulation of TRPC6 in Diabetic Nephropathy |
| title_short | Tacrolimus Protects Podocytes from Apoptosis via Downregulation of TRPC6 in Diabetic Nephropathy |
| title_sort | tacrolimus protects podocytes from apoptosis via downregulation of trpc6 in diabetic nephropathy |
| url | http://dx.doi.org/10.1155/2021/8832114 |
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