Islet transplantation promotes podocyte regeneration in a model of diabetic nephropathy

Abstract

IntroductionDiabetic nephropathy (DN) is the most common cause of end-stage renal disease (ESRD) and accounts for more than 25% of all ESRD cases in China (1,2). The initiation and progression of DN is associated with podocyte injury and loss. It has been reported that the podocyte population can be restored and that this process is linked to the regression of DN (3).Islet transplantation (IT) and pancreas transplantation are the most effective measures to counteract type 1 diabetes (4,5). It has been reported that IT can ameliorate albuminuria and alleviate damage to the kidney (6). We have previously demonstrated that IT can directly modify the barrier of glomerular filtration by ameliorating damage to the podocytes and the glomeruli basement membrane (7). However, the mechanisms that underlie how the barrier for glomerular filtration improves currently remain elusive.Recent studies have demonstrated that podocytes can regenerate from parietal epithelial cell (PEC) progenitors in human DN and in a diabetic mouse model (8,9).In this study, we examined whether IT induces PECs to express podocyte proteins. The amelioration of the structure and function of podocytes is a crucial factor in the process of recovery of early diabetic nephropathy. Thus, an increased focus on podocytes may be beneficial in the treatment of DN in clinical practice. Materials and methods AnimalsThis experimental study was conducted at Wenzhou Medical University. Thirty-six male Sprague Dawley (SD) rats at 8 weeks of age (body weight: 200-220 g) were obtained from the Laboratory Animal Center of Wenzhou Medical University. Eighteen of these rats were used to establish the DN models and the others were used as donor rats. All rats were housed with a 12:12-h light/dark cycle Background/aim: The purpose of this study was to observe whether islet transplantation could induce glomerular parietal epithelial cells to express podocyte proteins in a rat model of streptozotocin-induced diabetic nephropathy (DN). Materials and methods:A total of 18 rats were given single injections of streptozotocin to induce a DN model. Eight weeks after the modeling, successfully established DN rats were divided into three groups: an untreated group (DN group), an islet-transplanted group (IT group), and an insulin group (IN group). The islets cells were isolated from donor rats and surgically transplanted from under the kidney capsule in the IT group. Four weeks after treatment, pathological changes in the kidney were observed by pathological staining and electron microscopy. Immunohistochemical staining for PAX-2, Ki-67, and synaptopodin was performed to evaluate cell proliferation in the kidney tissues.Results: After 4 weeks of treatment, islet transplantation significantly alleviated damage to the podocytes and increased the number of glomerular transition cells compared to the DN and IN groups, which were defined as cells that double-stained for PAX-2 and synaptopodin in membranous nephropathy. The results of HE staining, PAS staining, and electron microscopy d...

The recruitment mechanisms and potential therapeutic targets of podocytes from parietal epithelial cells

“…Interestingly, the remission of podocyte loss is closely related to the differentiation of PECs into podocytes [ 33 , 35 , 36 ]. When many podocytes are lost, PECs can migrate to the capillary loops, and phenotypic changes occur.…”

Let‑7a‑5p may participate in the pathogenesis of diabetic nephropathy through targeting HMGA2

“…DN eventually leads to the development of chronic renal failure, which may seriously affect the quality of life of patients (5–7). At present, anti-DN therapies include the control of blood glucose and blood pressure, and the inhibition of the renin-angiotensin system; however, these methods only delay the progression of DN; such therapies are not able to reverse the progression of DN to the stages of renal function failure (7–9). Therefore, there is an urgent requirement to identify novel therapeutic targets for the management and prevention of DN.…”