Root of Polygonum cuspidatum extract reduces progression of diabetes-induced mesangial cell dysfunction via inhibition of platelet-derived growth factor-BB (PDGF-BB) and interaction with its receptor in streptozotocin-induced diabetic rats.

Eunjin Sohn,Yun Mi Lee,Junghyun Kim,Chan-Sik Kim,Kyuhyung Jo,Jin Sook Kim

doi:10.1186/1472-6882-14-477

Abstract

BackgroundPlatelet-derived growth factor–BB (PDGF-BB) is highly expressed in the renal tissues of patients with diabetic nephropathy, and it plays an important role in the initiation and progression of diabetic nephropathy. The aim of this study was to evaluate the protective effects of root of Polygonum cuspidatum extract (PCE) on early renal glomerular proliferation in streptozotocin (STZ)-induced diabetic rats.MethodsPCE (100, 350 mg/kg/day) was administered to diabetic rats for 16 weeks. Blood glucose and albuminuria were measured. Renal histology, α-smooth muscle actin (α-SMA), and proliferating cell nuclear antigen (PCNA) expression levels were also examined.ResultsAfter 16 weeks of treatment with PCE, severe hyperglycemia and albuminuria were observed in the diabetic rats. The expressions levels of α-SMA and PCNA proteins were significantly increased in the glomeruli of the diabetic rats. The expression levels of PDGF-BB and its receptor expressions were greatly increased in the glomeruli of the diabetic rats. However, PCE markedly reduced albuminuria in the diabetic rats. PCE inhibited α-SMA and PCNA up-regulation and ameliorated PDGF-BB and PEGFR-ß protein expression in the diabetic rats. In addition, the binding of PDGF-BB/PDGFR-ß was inhibited by PCE as shown by an in vitro assay.ConclusionsThese results suggest that PCE has an inhibitory effect on mesangial proliferation in diabetic renal tissues via the inhibition of the interaction of PDGF-BB with its receptor. PCE may have beneficial effects in preventing the progression of diabetic nephropathy.Electronic supplementary materialThe online version of this article (doi:10.1186/1472-6882-14-477) contains supplementary material, which is available to authorized users.

Highlights

Platelet-derived growth factor–BB (PDGF-BB) is highly expressed in the renal tissues of patients with diabetic nephropathy, and it plays an important role in the initiation and progression of diabetic nephropathy
Diabetic nephropathy causes the majority of case of end-stage renal disease, and it is an important cause of increased mortality in patients with diabetes mellitus (DM) worldwide
The general understanding of the pathogenic factors leading to renal fibrosis in diabetic nephropathy patients has considerably expanded, and the mechanisms involving TGF-ß and α-smooth muscle actin (α-SMA) have been found to be important to the development of diabetic renal fibrosis [17,18,19]

Summary

Introduction

Platelet-derived growth factor–BB (PDGF-BB) is highly expressed in the renal tissues of patients with diabetic nephropathy, and it plays an important role in the initiation and progression of diabetic nephropathy. The aim of this study was to evaluate the protective effects of root of Polygonum cuspidatum extract (PCE) on early renal glomerular proliferation in streptozotocin (STZ)-induced diabetic rats. Platelet-derived growth factor (PDGF) has been suggested to play a role in the pathophysiology renal tissues and plays important role in the initiation and progression of diabetic nephropathy [6]. It has been widely used as a medicinal herb for a variety of purposes in Asian countries, such as the treatment of inflammatory diseases, hepatitis, tumors, and diarrhea [11]. In this study, we investigated the protective effect of an ethanol extract of P. cuspidatum (PCE) against renal injury and fibrosis in STZ-induced diabetic rats

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