Islet transplantation promotes podocyte regeneration in a model of diabetic nephropathy

Diabetic nephropathy (DN) is a serious microvascular complication of diabetes. Compared with other therapies for diabetic patients, islet transplantation can effectively prevent and reverse diabetes-induced microvascular disease, such as diabetic retinopathy and nephropathy. PTX3 is the only long pentraxin that can be detected in renal tissue. In this study, we investigated the expression of PTX3 when early DN was reversed after islet transplantation.Methods. Diabetes was induced in rats by injecting streptozotocin (STZ). Twelve weeks later, the diabetic rats were divided into 2 groups: the islet transplantation group (IT) and the diabetic nephropathy group (DN). Renal injury, renal function, and the expression of PTX3 in the plasma and the kidneys were assessed with urinalysis, immunohistochemical staining, and Western blot, respectively.Results. The expression of PTX3 in the kidney was significantly decreased in the DN group but increased in the IT group because of the reversal of DN.Conclusions. Our data showed that the level of PTX3 in renal tissue is closely related to renal injury in DN. This may be used to quantify the extent of renal injury in DN, provide a potential early indicator of renal tubular injury in early DN patients, and assess DN clinical progression.

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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 ◽

10.1155/2021/9570405 ◽

2021 ◽

Vol 2021 ◽

pp. 1-11

Author(s):

Chongchu Huang ◽

Yi Zhou ◽

Hongjian Huang ◽

Yushu Zheng ◽

Lijun Kong ◽

...

Keyword(s):

Diabetic Nephropathy ◽

Signaling Pathways ◽

Signaling Pathway ◽

Islet Transplantation ◽

High Glucose ◽

Islet Cells ◽

Inflammatory Factors ◽

Efficacy Evaluation ◽

Podocyte Injury ◽

Expression Levels

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.

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Combined Microencapsulated Islet Transplantation and Revascularization of Aortorenal Bypass in a Diabetic Nephropathy Rat Model

Journal of Diabetes Research ◽

10.1155/2016/9706321 ◽

2016 ◽

Vol 2016 ◽

pp. 1-8 ◽

Cited By ~ 1

Author(s):

Yunqiang He ◽

Ziqiang Xu ◽

Hongxing Fu ◽

Bin Chen ◽

Silu Wang ◽

...

Keyword(s):

Diabetic Nephropathy ◽

Blood Glucose ◽

Islet Transplantation ◽

Rat Model ◽

Good Control ◽

Protective Effects ◽

Urine Protein ◽

Monocyte Chemoattractant Protein 1 ◽

Filtration Barrier ◽

Combined Strategy

Objective.Revascularization of aortorenal bypass is a preferred technique for renal artery stenosis (RAS) in diabetic nephropathy (DN) patients. Restenosis of graft vessels also should be considered in patients lacking good control of blood glucose. In this study, we explored a combined strategy to prevent the recurrence of RAS in the DN rat model.Methods.A model of DN was established by intraperitoneal injection of streptozotocin. Rats were divided into 4 groups: SR group, MIT group, Com group, and the untreated group. The levels of blood glucose and urine protein were measured, and changes in renal pathology were observed. The expression of monocyte chemoattractant protein-1 (MCP-1) in graft vessels was assessed by immunohistochemical staining. Histopathological staining was performed to assess the pathological changes of glomeruli and tubules.Results.The levels of urine protein and the expression of MCP-1 in graft vessels were decreased after islet transplantation. The injury of glomerular basement membrane and podocytes was significantly ameliorated.Conclusions.The combined strategy of revascularization and microencapsulated islet transplantation had multiple protective effects on diabetic nephropathy, including preventing atherosclerosis in the graft vessels and alleviating injury to the glomerular filtration barrier. This combined strategy may be helpful for DN patients with RAS.

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Aberrant activation of Notch-1 signaling inhibits podocyte restoration after islet transplantation in a rat model of diabetic nephropathy

Cell Death and Disease ◽

10.1038/s41419-018-0985-z ◽

2018 ◽

Vol 9 (10) ◽

Cited By ~ 5

Author(s):

Yunqiang He ◽

Mei Zhang ◽

Ying Wu ◽

Hemin Jiang ◽

Hongxing Fu ◽

...

Keyword(s):

Diabetic Nephropathy ◽

Islet Transplantation ◽

Rat Model ◽

Notch 1

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C-peptide and islet transplantation improve glomerular filtration barrier in diabetic nephropathy rats

Transplant Immunology ◽

10.1016/j.trim.2020.101322 ◽

2020 ◽

Vol 62 ◽

pp. 101322

Author(s):

Xiaojie Ni ◽

Ziqiang Xu ◽

Jinjun Wang ◽

Shaoling Zheng ◽

Yong Cai

Keyword(s):

Diabetic Nephropathy ◽

Glomerular Filtration ◽

Islet Transplantation ◽

Glomerular Filtration Barrier ◽

C Peptide ◽

Filtration Barrier

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Reversal of Early Diabetic Nephropathy by Islet Transplantation under the Kidney Capsule in a Rat Model

Journal of Diabetes Research ◽

10.1155/2016/4157313 ◽

2016 ◽

Vol 2016 ◽

pp. 1-12 ◽

Cited By ~ 3

Author(s):

Yunqiang He ◽

Ziqiang Xu ◽

Mingshi Zhou ◽

Minmin Wu ◽

Xuehai Chen ◽

...

Keyword(s):

Diabetes Mellitus ◽

Diabetic Nephropathy ◽

Basement Membrane ◽

Islet Transplantation ◽

Rat Model ◽

Treated Group ◽

Diabetic Patients ◽

Creatinine Ratio ◽

Membrane Structures ◽

Filtration Barrier

Objective. Diabetic nephropathy (DN) is a common microvascular complication of diabetes mellitus, and insulin therapy has many side effects in the treatment of DN. Islet transplantation has emerged as a promising therapy for diabetic patients. This study was established to investigate its advantageous effects in a rat model of early DN.Methods. Streptozotocin was administered to the rats to induce diabetes. Twelve weeks later, the diabetic rats were divided into 3 groups: the islet-transplanted group (IT group), the insulin-treated group (IN group), and the untreated group (DN group). Renal injury and kidney structure were assessed by urinalysis and transmission electron microscopy (TEM) detection. Immunohistochemical staining and western blotting were performed to assess renal fibrosis levels.Results. The early DN features were reversed and the glomerular filtration barrier and basement membrane structures were improved at 4 weeks after islet transplantation. The urine microalbumin-to-creatinine ratio (ACR), protein-to-creatinine ratio, and mean thickness of the glomerular basement membrane (GBM) were significantly decreased in the IT group. The expression of renal fibrotic factors was also significantly decreased.Conclusions. These data suggest that early DN can be reversed after islet transplantation, and they may facilitate the development of a clinical therapeutic strategy for human diabetes mellitus.

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