Background: Accumulating evidence suggests that vitamin D and its analogs reduce proteinuria and slow the decline in kidney function in chronic kidney disease. Given a rich literature identifying podocyte apoptosis as an early step in the pathophysiological progression to proteinuria and glomerulosclerosis, we hypothesized that vitamin D protects podocytes from undergoing apoptosis. Methods: A rat model of podocyte apoptosis was created by a single intravenous injection of 100 mg·kg^–1 puromycin aminonucleoside (PAN) and received either solvent or 1,25(OH)₂D₃ treatment. Proteinuria, podocyte apoptosis, the expression of nephrin protein and mRNA, TGF-β/Smad and phosphatidylinositol 3-kinase (PI3K)/Akt-signaling pathway were evaluated, respectively. Results: PAN induced massive proteinuria, serum creatinine elevation and podocyte apoptosis in PAN nephropathy rats, which was associated with the loss of nephrin, an adhesion molecule specific for the glomerular slit and the reduced of p-Akt/Akt ratio. Moreover, PAN induced foot process retraction, redistribution of nephrin and the activation of TGF-β/Smad-signaling pathway. Compared with PAN nephropathy rats, 1,25(OH)₂D₃ significantly prevented loss of nephrin, foot process retraction and podocyte apoptosis by stimulating Akt phosphorylation and suppressing TGF-β/Smad-signaling pathway. Conclusion: 1,25(OH)₂D₃ reduced the PAN-induced podocyte apoptosis and loss of nephrin in PAN nephropathy rat. The anti-apoptotic effects of 1,25(OH)₂D₃ on podocytes may be partly attributable to activation of a PI3K/Akt survival pathway.

Renal cell carcinoma (RCC) accounts for 3% of all cancer-related mortalities in adults. The risk factors for the development of RCC remain under investigation. Vascular endothelial growth factor (VEGF) is a key mediator of angiogenesis and is crucial for the development and metastasis of tumors, including RCC. VEGF gene polymorphisms may alter VEGF protein concentrations, affect the process of angiogenesis and may be involved in inter-individual variation in carcinogenesis. In the present study, a systematic review and meta-analysis were performed based on published case-control studies in order to estimate the association between VEGF gene polymorphisms and the susceptibility to RCC. A total of five studies that involved eight polymorphisms and were published between January 2000 and December 2012 were identified from PubMed. The results of this systematic review and meta-analysis indicate that the VEGF 936C/T, 1612G/A, −1154G/A, −2549I/D, −460T/C and 405G/C gene polymorphisms are not associated with the risk of RCC. There was no polymorphism in 702C/T and RCC and the −2578C/A gene polymorphism may be associated with an increased risk of RCC. However, due to the limitations of the present study, further high quality case-control studies are warranted to confirm these findings.

Abstract. Diabetic nephropathy (DN) is a major cause of end-stage renal disease, in which the SMAD signaling pathway plays an important role. The aim of the present study was to identify differentially expressed microRNAs (miRNAs) during the progression of DN and to investigate a selected miRNA in relation to SMAD3/4 and its therapeutic efficacy. The miRNA microarray was used to identify differentially expressed miRNAs in db/db DN mice. Reverse transcription-quantitative polymerase chain reaction and immunoblot analyses were used to detect SMAD3/4 expression. The development of DN in the db/db mice was demonstrated by glucose dysregulation and typical morphological changes in the kidney. miRNA-346 (miR-346) was identified as one of the differentially expressed miRNAs. The expression of SMAD3/4 was significantly attenuated by miR-346 administration and the therapeutic effects of miR-346 were observed in the DN mouse models. miR-346 was identified as a negative regulator of SMAD3/4. SMAD3/4 was upregulated in the renal tissue of db/db mice. The administration of miR-346 attenuated the SMAD3/4 expression in renal tissue and ameliorated the renal function and glomerular histology in DN mice. This study paves the way for clinical studies of miR-346 in DN. IntroductionDiabetes is the most prevalent disease worldwide. According to the World Health Organization, ~9.5% of the adult population (~347 million individuals) were suffering from diabetes in 2008, and the number is expected to double by 2030 (1). As one of the major complications of diabetes, diabetic nephropathy (DN) is now the most common cause of end-stage renal disease, particularly in Western countries (2). Hypertension and poor glycemic control are the major clinical associations that frequently precede overt DN (3). In clinical terms, the condition is characterized by the development of proteinuria, specifically albuminuria, with a subsequent reduction in the glomerular filtration rate. DN can progress over a period of 10-20 years; if left untreated, the resulting uremia is fatal (4). The histological characteristics of DN include mesangial expansion, thickening of the glomerular basement membrane and podocyte effacement, in addition to glomerular sclerosis (5,6). DN is one of the direct causes of mortality in diabetic patients. The db/db mouse is an obese hyperinsulinemic model of genetic diabetes. This animal model develops abnormalities in renal function and renal morphology that parallel those in the nephropathy of patients with type 2 diabetes (7); therefore, the db/db mouse is a useful animal model for investigating the pathophysiology of DN and exploring an effective therapy for the disease.During the past two decades, a novel class of non-coding RNA, microRNAs (miRNAs), has been found to be expressed in all tissues and to play essential roles in tissue homeostasis and disease progression (8,9). miRNAs are endogenous, single-stranded RNA molecules of ~22 nucleotides in length that regulate target mRNAs at the post-transcriptional level via base-pai...