Chongchu Huang1, Yi Zhou1, Hongjian Huang1, Yushu Zheng1, Lijun Kong1, Hewei Zhang1, Yan Zhang2, Hongwei Wang1, Mei Yang3, Xiaona Xu4, Bicheng Chen1. 1. Key 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, China. 2. Transplantation Centre, The First Affiliated Hospital of Wenzhou Medical University, 325015 Wenzhou, Zhejiang Province, China. 3. Intensive Care Unit, The First Affiliated Hospital of Wenzhou Medical University, 325015 Wenzhou, Zhejiang Province, China. 4. Operating Room, The First Affiliated Hospital of Wenzhou Medical University, 325015 Wenzhou, Zhejiang Province, China.
Abstract
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.
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.
Authors: Paolo Fiorina; Andrea Vergani; Roberto Bassi; Monika A Niewczas; Mehmet M Altintas; Marcus G Pezzolesi; Francesca D'Addio; Melissa Chin; Sara Tezza; Moufida Ben Nasr; Deborah Mattinzoli; Masami Ikehata; Domenico Corradi; Valerie Schumacher; Lisa Buvall; Chih-Chuan Yu; Jer-Ming Chang; Stefano La Rosa; Giovanna Finzi; Anna Solini; Flavio Vincenti; Maria Pia Rastaldi; Jochen Reiser; Andrzej S Krolewski; Peter H Mundel; Mohamed H Sayegh Journal: J Am Soc Nephrol Date: 2014-03-27 Impact factor: 10.121
Authors: J J Li; S J Kwak; D S Jung; J-J Kim; T-H Yoo; D-R Ryu; S H Han; H Y Choi; J E Lee; S J Moon; D K Kim; D S Han; S-W Kang Journal: Kidney Int Suppl Date: 2007-08 Impact factor: 10.545