Islet Transplantation Reverses Podocyte Injury in Diabetic Nephropathy or Induced by High Glucose via Inhibiting RhoA/ROCK/NF-κB Signaling Pathway
Objective. Abnormal signaling pathways play a crucial role in the mechanisms of podocyte injury in diabetic nephropathy. They also affect the recovery of podocytes after islet transplantation (IT). However, the specific signaling abnormalities that affect the therapeutic effect of IT on podocytes re...
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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/10.1155/2021/9570405 |
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| author | Chongchu Huang Yi Zhou Hongjian Huang Yushu Zheng Lijun Kong Hewei Zhang Yan Zhang Hongwei Wang Mei Yang Xiaona Xu Bicheng Chen |
| author_facet | Chongchu Huang Yi Zhou Hongjian Huang Yushu Zheng Lijun Kong Hewei Zhang Yan Zhang Hongwei Wang Mei Yang Xiaona Xu Bicheng Chen |
| author_sort | Chongchu Huang |
| collection | DOAJ |
| description | Objective. Abnormal signaling pathways play a crucial role in the mechanisms of podocyte injury in diabetic nephropathy. They also affect the recovery of podocytes after islet transplantation (IT). However, the specific signaling abnormalities that affect the therapeutic effect of IT on podocytes remains unclear. The purpose of this study was to assess whether the RhoA/ROCK/NF-κB signaling pathway is related to podocyte restoration after IT. Methods. A mouse model of diabetic nephropathy was established in vivo using streptozotocin. The mice were then subsequently reared for 4 weeks after islet transplantation to determine the effect of IT. Islet cells, CCG-1423 (RhoA Inhibitor), and fasudil (ROCK inhibitor) were then cocultured with podocytes in vitro to assess their protective effects on podocyte injury induced by high glucose (HG). Protein expression levels of RhoA, ROCK1, synaptopodin, IL-6, and MCP-1 in kidney tissues were then measured using immunohistochemistry and Western blotting techniques. Results. Islet transplantation reduced the expression levels of RhoA/ROCK1 and that of related inflammatory factors such as IL-6 and MCP-1 in the kidney podocytes of diabetic nephropathy. In the same line, islet cells reduced the expression of RhoA, ROCK1, and pp65 in immortalized podocytes under high glucose (35.0 mmol/L glucose) conditions. Conclusions. Islet transplantation can reverse podocyte injury in diabetes nephropathy by inhibiting the RhoA/ROCK1 signaling pathway. Islet cells have a strong protective effect on podocytes treated with high glucose (35.0 mmol/L glucose). Discovery of signaling pathways affecting podocyte recovery is helpful for individualized efficacy evaluation and targeted therapy of islet transplantation patients. |
| format | Article |
| id | doaj-art-052ca8b4e7f24fca8627708c7431571e |
| 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-052ca8b4e7f24fca8627708c7431571e2025-02-03T01:20:44ZengWileyJournal of Diabetes Research2314-67452314-67532021-01-01202110.1155/2021/95704059570405Islet Transplantation Reverses Podocyte Injury in Diabetic Nephropathy or Induced by High Glucose via Inhibiting RhoA/ROCK/NF-κB Signaling PathwayChongchu Huang0Yi Zhou1Hongjian Huang2Yushu Zheng3Lijun Kong4Hewei Zhang5Yan Zhang6Hongwei Wang7Mei Yang8Xiaona Xu9Bicheng Chen10Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000 Zhejiang Province, ChinaKey Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000 Zhejiang Province, ChinaKey Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000 Zhejiang Province, ChinaKey Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000 Zhejiang Province, ChinaKey Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000 Zhejiang Province, ChinaKey Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000 Zhejiang Province, ChinaTransplantation Centre, The First Affiliated Hospital of Wenzhou Medical University, 325015 Wenzhou, Zhejiang Province, ChinaKey Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000 Zhejiang Province, ChinaIntensive Care Unit, The First Affiliated Hospital of Wenzhou Medical University, 325015 Wenzhou, Zhejiang Province, ChinaOperating Room, The First Affiliated Hospital of Wenzhou Medical University, 325015 Wenzhou, Zhejiang Province, ChinaKey Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000 Zhejiang Province, ChinaObjective. Abnormal signaling pathways play a crucial role in the mechanisms of podocyte injury in diabetic nephropathy. They also affect the recovery of podocytes after islet transplantation (IT). However, the specific signaling abnormalities that affect the therapeutic effect of IT on podocytes remains unclear. The purpose of this study was to assess whether the RhoA/ROCK/NF-κB signaling pathway is related to podocyte restoration after IT. Methods. A mouse model of diabetic nephropathy was established in vivo using streptozotocin. The mice were then subsequently reared for 4 weeks after islet transplantation to determine the effect of IT. Islet cells, CCG-1423 (RhoA Inhibitor), and fasudil (ROCK inhibitor) were then cocultured with podocytes in vitro to assess their protective effects on podocyte injury induced by high glucose (HG). Protein expression levels of RhoA, ROCK1, synaptopodin, IL-6, and MCP-1 in kidney tissues were then measured using immunohistochemistry and Western blotting techniques. Results. Islet transplantation reduced the expression levels of RhoA/ROCK1 and that of related inflammatory factors such as IL-6 and MCP-1 in the kidney podocytes of diabetic nephropathy. In the same line, islet cells reduced the expression of RhoA, ROCK1, and pp65 in immortalized podocytes under high glucose (35.0 mmol/L glucose) conditions. Conclusions. Islet transplantation can reverse podocyte injury in diabetes nephropathy by inhibiting the RhoA/ROCK1 signaling pathway. Islet cells have a strong protective effect on podocytes treated with high glucose (35.0 mmol/L glucose). Discovery of signaling pathways affecting podocyte recovery is helpful for individualized efficacy evaluation and targeted therapy of islet transplantation patients.http://dx.doi.org/10.1155/2021/9570405 |
| spellingShingle | Chongchu Huang Yi Zhou Hongjian Huang Yushu Zheng Lijun Kong Hewei Zhang Yan Zhang Hongwei Wang Mei Yang Xiaona Xu Bicheng Chen Islet Transplantation Reverses Podocyte Injury in Diabetic Nephropathy or Induced by High Glucose via Inhibiting RhoA/ROCK/NF-κB Signaling Pathway Journal of Diabetes Research |
| title | Islet Transplantation Reverses Podocyte Injury in Diabetic Nephropathy or Induced by High Glucose via Inhibiting RhoA/ROCK/NF-κB Signaling Pathway |
| title_full | Islet Transplantation Reverses Podocyte Injury in Diabetic Nephropathy or Induced by High Glucose via Inhibiting RhoA/ROCK/NF-κB Signaling Pathway |
| title_fullStr | Islet Transplantation Reverses Podocyte Injury in Diabetic Nephropathy or Induced by High Glucose via Inhibiting RhoA/ROCK/NF-κB Signaling Pathway |
| title_full_unstemmed | Islet Transplantation Reverses Podocyte Injury in Diabetic Nephropathy or Induced by High Glucose via Inhibiting RhoA/ROCK/NF-κB Signaling Pathway |
| title_short | Islet Transplantation Reverses Podocyte Injury in Diabetic Nephropathy or Induced by High Glucose via Inhibiting RhoA/ROCK/NF-κB Signaling Pathway |
| title_sort | islet transplantation reverses podocyte injury in diabetic nephropathy or induced by high glucose via inhibiting rhoa rock nf κb signaling pathway |
| url | http://dx.doi.org/10.1155/2021/9570405 |
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