title: Reversal of Early Diabetic Nephropathy by Islet Transplantation under the Kidney Capsule in a Rat Model.
abstract: 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.
authors.affiliation: Key Laboratory of Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
authors.forename: Yunqiang
authors.identifier: 0000-0002-4216-8931
authors.initials: Y
authors.lastname: He
authors.affiliation: Department of Transplantation, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province 325000, China.
authors.forename: Ziqiang
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Key Laboratory of Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
authors.forename: Mingshi
authors.initials: M
authors.lastname: Zhou
authors.affiliation: Key Laboratory of Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
authors.forename: Minmin
authors.initials: M
authors.lastname: Wu
authors.affiliation: Key Laboratory of Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
authors.forename: Xuehai
authors.initials: X
authors.lastname: Chen
authors.affiliation: Key Laboratory of Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
authors.forename: Silu
authors.initials: S
authors.lastname: Wang
authors.affiliation: School of Pharmacy, Wenzhou Medical University, Wenzhou, Zhejiang Province 325000, China.
authors.forename: Kaiyan
authors.initials: K
authors.lastname: Qiu
authors.affiliation: Department of Transplantation, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province 325000, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Cai
authors.affiliation: School of Pharmacy, Wenzhou Medical University, Wenzhou, Zhejiang Province 325000, China.
authors.forename: Hongxing
authors.initials: H
authors.lastname: Fu
authors.affiliation: Key Laboratory of Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
authors.forename: Bicheng
authors.identifier: 0000-0002-5663-7065
authors.initials: B
authors.lastname: Chen
authors.affiliation: Department of Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
authors.forename: Mengtao
authors.identifier: 0000-0002-3498-5034
authors.initials: M
authors.lastname: Zhou
mesh_terms: D000419:Albuminuria; D000818:Animals; D018932:Chemokine CCL2 / Q000378:metabolism; D055513:Connective Tissue Growth Factor / Q000378:metabolism; D003404:Creatinine / Q000652:urine; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000628:therapy*; D003928:Diabetic Nephropathies / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D005355:Fibrosis; D050533:Glomerular Basement Membrane / Q000648:ultrastructure; D017228:Hepatocyte Growth Factor / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007150:Immunohistochemistry; D007328:Insulin / Q000627:therapeutic use; D016381:Islets of Langerhans Transplantation / Q000379:methods*; D007668:Kidney / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D008297:Male; D046529:Microscopy, Electron, Transmission; D050199:Podocytes / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: C526316:CCN2 protein, rat; C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D007004:Hypoglycemic Agents; D007328:Insulin; C508962:Tgfb1 protein, rat; D053773:Transforming Growth Factor beta1; D055513:Connective Tissue Growth Factor; D017228:Hepatocyte Growth Factor; D003404:Creatinine