Triptolide protects against podocyte injury in diabetic nephropathy by activating the Nrf2/HO-1 pathway and inhibiting the NLRP3 inflammasome pathway
Objectives Diabetic nephropathy (DN) is the most common microvascular complication of diabetes mellitus. This study investigated the mechanism of triptolide (TP) in podocyte injury in DN.Methods DN mouse models were established by feeding with a high-fat diet and injecting with streptozocin and MPC5...
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Taylor & Francis Group
2023-12-01
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| Series: | Renal Failure |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/0886022X.2023.2165103 |
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| author | Chenlei Lv Tianyang Cheng Bingbing Zhang Ke Sun Keda Lu |
| author_facet | Chenlei Lv Tianyang Cheng Bingbing Zhang Ke Sun Keda Lu |
| author_sort | Chenlei Lv |
| collection | DOAJ |
| description | Objectives Diabetic nephropathy (DN) is the most common microvascular complication of diabetes mellitus. This study investigated the mechanism of triptolide (TP) in podocyte injury in DN.Methods DN mouse models were established by feeding with a high-fat diet and injecting with streptozocin and MPC5 podocyte injury models were induced by high-glucose (HG), followed by TP treatment. Fasting blood glucose and renal function indicators, such as 24 h urine albumin (UAlb), serum creatinine (SCr), blood urea nitrogen (BUN), and kidney/body weight ratio of mice were examined. H&E and TUNEL staining were performed for evaluating pathological changes and apoptosis in renal tissue. The podocyte markers, reactive oxygen species (ROS), oxidative stress (OS), serum inflammatory cytokines, nuclear factor-erythroid 2-related factor 2 (Nrf2) pathway-related proteins, and pyroptosis were detected by Western blotting and corresponding kits. MPC5 cell viability and pyroptosis were evaluated by MTT and Hoechst 33342/PI double-fluorescence staining. Nrf2 inhibitor ML385 was used to verify the regulation of TP on Nrf2.Results TP improved renal function and histopathological injury of DN mice, alleviated podocytes injury, reduced OS and ROS by activating the Nrf2/heme oxygenase-1 (HO-1) pathway, and weakened pyroptosis by inhibiting the nod-like receptor (NLR) family pyrin domain containing 3 (NLRP3) inflammasome pathway. In vitro experiments further verified the inhibition of TP on OS and pyroptosis by mediating the Nrf2/HO-1 and NLRP3 inflammasome pathways. Inhibition of Nrf2 reversed the protective effect of TP on MPC5 cells.Conclusions Overall, TP alleviated podocyte injury in DN by inhibiting OS and pyroptosis via Nrf2/ROS/NLRP3 axis. |
| format | Article |
| id | doaj-art-b7d3490df8a543f08fb06fdba2603df7 |
| institution | OA Journals |
| issn | 0886-022X 1525-6049 |
| language | English |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Renal Failure |
| spelling | doaj-art-b7d3490df8a543f08fb06fdba2603df72025-08-20T02:28:53ZengTaylor & Francis GroupRenal Failure0886-022X1525-60492023-12-0145110.1080/0886022X.2023.2165103Triptolide protects against podocyte injury in diabetic nephropathy by activating the Nrf2/HO-1 pathway and inhibiting the NLRP3 inflammasome pathwayChenlei Lv0Tianyang Cheng1Bingbing Zhang2Ke Sun3Keda Lu4Department of Nephrology, The First Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, ChinaDepartment of Nephrology, The First Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, ChinaCollege of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, ChinaDepartment of Nephrology, The First Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, ChinaDepartment of Nephrology, The Third Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, ChinaObjectives Diabetic nephropathy (DN) is the most common microvascular complication of diabetes mellitus. This study investigated the mechanism of triptolide (TP) in podocyte injury in DN.Methods DN mouse models were established by feeding with a high-fat diet and injecting with streptozocin and MPC5 podocyte injury models were induced by high-glucose (HG), followed by TP treatment. Fasting blood glucose and renal function indicators, such as 24 h urine albumin (UAlb), serum creatinine (SCr), blood urea nitrogen (BUN), and kidney/body weight ratio of mice were examined. H&E and TUNEL staining were performed for evaluating pathological changes and apoptosis in renal tissue. The podocyte markers, reactive oxygen species (ROS), oxidative stress (OS), serum inflammatory cytokines, nuclear factor-erythroid 2-related factor 2 (Nrf2) pathway-related proteins, and pyroptosis were detected by Western blotting and corresponding kits. MPC5 cell viability and pyroptosis were evaluated by MTT and Hoechst 33342/PI double-fluorescence staining. Nrf2 inhibitor ML385 was used to verify the regulation of TP on Nrf2.Results TP improved renal function and histopathological injury of DN mice, alleviated podocytes injury, reduced OS and ROS by activating the Nrf2/heme oxygenase-1 (HO-1) pathway, and weakened pyroptosis by inhibiting the nod-like receptor (NLR) family pyrin domain containing 3 (NLRP3) inflammasome pathway. In vitro experiments further verified the inhibition of TP on OS and pyroptosis by mediating the Nrf2/HO-1 and NLRP3 inflammasome pathways. Inhibition of Nrf2 reversed the protective effect of TP on MPC5 cells.Conclusions Overall, TP alleviated podocyte injury in DN by inhibiting OS and pyroptosis via Nrf2/ROS/NLRP3 axis.https://www.tandfonline.com/doi/10.1080/0886022X.2023.2165103Diabetic nephropathyMPC5triptolideNLRP3 inflammasomeNrf2oxidative stress |
| spellingShingle | Chenlei Lv Tianyang Cheng Bingbing Zhang Ke Sun Keda Lu Triptolide protects against podocyte injury in diabetic nephropathy by activating the Nrf2/HO-1 pathway and inhibiting the NLRP3 inflammasome pathway Renal Failure Diabetic nephropathy MPC5 triptolide NLRP3 inflammasome Nrf2 oxidative stress |
| title | Triptolide protects against podocyte injury in diabetic nephropathy by activating the Nrf2/HO-1 pathway and inhibiting the NLRP3 inflammasome pathway |
| title_full | Triptolide protects against podocyte injury in diabetic nephropathy by activating the Nrf2/HO-1 pathway and inhibiting the NLRP3 inflammasome pathway |
| title_fullStr | Triptolide protects against podocyte injury in diabetic nephropathy by activating the Nrf2/HO-1 pathway and inhibiting the NLRP3 inflammasome pathway |
| title_full_unstemmed | Triptolide protects against podocyte injury in diabetic nephropathy by activating the Nrf2/HO-1 pathway and inhibiting the NLRP3 inflammasome pathway |
| title_short | Triptolide protects against podocyte injury in diabetic nephropathy by activating the Nrf2/HO-1 pathway and inhibiting the NLRP3 inflammasome pathway |
| title_sort | triptolide protects against podocyte injury in diabetic nephropathy by activating the nrf2 ho 1 pathway and inhibiting the nlrp3 inflammasome pathway |
| topic | Diabetic nephropathy MPC5 triptolide NLRP3 inflammasome Nrf2 oxidative stress |
| url | https://www.tandfonline.com/doi/10.1080/0886022X.2023.2165103 |
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