Abstract. Diabetic nephropathy (DN) exhibits a deteriorating course that may lead to end-stage renal failure. Astragalosides have been clinically tested for the treatment of DN, but the mechanism is unclear at present. In this study, the effects of astragalosides were investigated on high glucose-induced proliferation and expression of transforming growth factor-β 1

Abstract. Diabetic nephropathy (DN) is one of the most important causes that leads to end-stage renal disease and the efficacy of strategies currently available for the prevention of DN remains unsatisfactory. Sitagliptin (SIT), which is a dipeptidyl peptidase-4 inhibitor, exhibited a modest beneficial effect on glycated hemoglobin levels and is capable of ameliorating renal ischemia reperfusion injury. By determining the expression of transforming growth factor-β1 (TGF-β1), connective tissue growth factor (CTGF), collagen type IV (ColIV) and fibronectin (FN) levels in high glucose-cultured glomerular mesangial cells (MCs), the present study aimed to assess the anti-proliferative and anti-fibrotic effects of SIT on the therapeutic potential for the prevention of DN and its mechanism. Specifically, cell proliferation was determined via cell counting kit-8 assay, and the expression levels of TGF-β1 and CTGF mRNA were detected by reverse transcription polymerase chain reaction analysis. Furthermore, the secretion of TGF-β1, CTGF, ColIV and FN proteins was measured via enzyme-linked immunosorbent assays. The results demonstrated that high glucose induced the proliferation of MCs and enhanced the expression of TGF-β1, CTGF, ColIV and FN. Furthermore, treatment with SIT inhibited cell proliferation and the expression of TGF-β1, CTGF, ColIV and FN induced by high glucose. In conclusion, SIT inhibits cell proliferation and the expression of the major extracellular matrix proteins induced by high glucose, indicating its value for treating or relieving DN. IntroductionDiabetic nephropathy (DN), which is the leading cause of end-stage kidney failure, is increasing worldwide (1). Mesangial expansion of DN, caused by the proliferation of mesangial cells (MCs) and the excessive accumulation of the extracellular matrix (ECM), is one of the pathological features of DN (2). Hyperglycemia, which activates multiple intracellular signaling factors and results in abnormalities in blood flow and the accumulation of ECM (3-5), has been confirmed as the main initiative factor in the etiology of DN (6), which is one type of kidney fibrosis disease (7-9). In the clinical settings, the major ECM proteins, including collagen type IV (ColIV) and fibronectin (FN), are regarded as the markers of fibrogenesis in numerous kidney fibrosis diseases, such as DN. However, transforming growth factor-β1 (TGF-β1) and its downstream mediator connective tissue growth factor (CTGF) are recognized as fibrogenic cytokines and have a decisive role in the kidney pathophysiology of DN (10,11). At present, MCs are considered as the main type of cells that secrete ECM (12). Therefore, inhibition of MC proliferation and ECM accumulation can be applied as a practical method to treat or delay DN.However, no therapies that are currently available are able to retard the progression of end-stage renal failure and novel treatments in the management of DN are therefore required. Sitagliptin (SIT) is one of the most well-known incretin enhancers or gliptins, which incre...