11
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Effects of Shen'an granules on Wnt signaling pathway in mouse models of diabetic nephropathy

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          The effect of Shen'an granules on the Wnt signaling pathway in renal tissues of mouse models of streptozotocin (STZ)-induced diabetic nephropathy was investigated in the present study. A total of 62 BALB/c mice were randomly divided into the normal control (A group), model (B group), losartan (C group), low-dose Shen'an granules (D group), and high-dose Shen'an granules (E group) groups. The mouse model of diabetic nephropathy was established by a single intraperitoneal injection of STZ (150 mg/kg). The animals were treated with drugs for 8 weeks, and blood creatinine, blood urea nitrogen, triglycerides (TG), and total cholesterol (CHOL) were measured prior to and after treatment. PAS staining was performed for observation of glomerular microstructure by light microscope, and western blot analysis was performed to detect Wnt1 protein and β-catenin protein. The results indicated that the quantification of 24-h microalbuminuria, and levels of blood creatinine, urea nitrogen, TG, and CHOL were significantly lower in the high- and low-dose Shen'an granules groups than those in the model group (p<0.05). The expression levels of Wnt1 protein and β-catenin protein in the high- and low-dose Shen'an granules groups were significantly lower than those in the model group (p<0.05). In conclusion, proteinuria, renal dysfunction, and dyslipidemias are closely associated with the abnormal activation of the Wnt signaling pathway in the mouse model of diabetic nephropathy. The mechanism by which Shen'an granules regulate proteinuria, renal function, and blood lipids may be associated with inhibition of the abnormally activated Wnt signaling pathway.

          Related collections

          Most cited references20

          • Record: found
          • Abstract: found
          • Article: found
          Is Open Access

          Transcriptome Analysis of Human Diabetic Kidney Disease

          OBJECTIVE Diabetic kidney disease (DKD) is the single leading cause of kidney failure in the U.S., for which a cure has not yet been found. The aim of our study was to provide an unbiased catalog of gene-expression changes in human diabetic kidney biopsy samples. RESEARCH DESIGN AND METHODS Affymetrix expression arrays were used to identify differentially regulated transcripts in 44 microdissected human kidney samples. DKD samples were significant for their racial diversity and decreased glomerular filtration rate (~25–35 mL/min). Stringent statistical analysis, using the Benjamini-Hochberg corrected two-tailed t test, was used to identify differentially expressed transcripts in control and diseased glomeruli and tubuli. Two different web-based algorithms were used to define differentially regulated pathways. RESULTS We identified 1,700 differentially expressed probesets in DKD glomeruli and 1,831 in diabetic tubuli, and 330 probesets were commonly differentially expressed in both compartments. Pathway analysis highlighted the regulation of Ras homolog gene family member A, Cdc42, integrin, integrin-linked kinase, and vascular endothelial growth factor signaling in DKD glomeruli. The tubulointerstitial compartment showed strong enrichment for inflammation-related pathways. The canonical complement signaling pathway was determined to be statistically differentially regulated in both DKD glomeruli and tubuli and was associated with increased glomerulosclerosis even in a different set of DKD samples. CONCLUSIONS Our studies have cataloged gene-expression regulation and identified multiple novel genes and pathways that may play a role in the pathogenesis of DKD or could serve as biomarkers.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Wnt/beta-catenin signaling promotes renal interstitial fibrosis.

            Wnts compose a family of signaling proteins that play an essential role in kidney development, but their expression in adult kidney is thought to be silenced. Here, we analyzed the expression and regulation of Wnts and their receptors and antagonists in normal and fibrotic kidneys after obstructive injury. In the normal mouse kidney, the vast majority of 19 different Wnts and 10 frizzled receptor genes was expressed at various levels. After unilateral ureteral obstruction, all members of the Wnt family except Wnt5b, Wnt8b, and Wnt9b were upregulated in the fibrotic kidney with distinct dynamics. In addition, the expression of most Fzd receptors and Wnt antagonists was also induced. Obstructive injury led to a dramatic accumulation of beta-catenin in the cytoplasm and nuclei of renal tubular epithelial cells, indicating activation of the canonical pathway of Wnt signaling. Numerous Wnt/beta-catenin target genes (c-Myc, Twist, lymphoid enhancer-binding factor 1, and fibronectin) were induced, and their expression was closely correlated with renal beta-catenin abundance. Delivery of the Wnt antagonist Dickkopf-1 gene significantly reduced renal beta-catenin accumulation and inhibited the expression of Wnt/beta-catenin target genes. Furthermore, gene therapy with Dickkopf-1 inhibited myofibroblast activation; suppressed expression of fibroblast-specific protein 1, type I collagen, and fibronectin; and reduced total collagen content in the model of obstructive nephropathy. In summary, these results establish a role for Wnt/beta-catenin signaling in the pathogenesis of renal fibrosis and identify this pathway as a potential therapeutic target.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Wnt/beta-catenin signaling promotes podocyte dysfunction and albuminuria.

              Podocyte dysfunction, one of the major causes of proteinuria, leads to glomerulosclerosis and end stage renal disease, but its underlying mechanism remains poorly understood. Here we show that Wnt/beta-catenin signaling plays a critical role in podocyte injury and proteinuria. Treatment with adriamycin induced Wnt and activated beta-catenin in mouse podocytes. Overexpression of Wnt1 in vivo activated glomerular beta-catenin and aggravated albuminuria and adriamycin-induced suppression of nephrin expression, whereas blockade of Wnt signaling with Dickkopf-1 ameliorated podocyte lesions. Podocyte-specific knockout of beta-catenin protected against development of albuminuria after injury. Moreover, pharmacologic activation of beta-catenin induced albuminuria in wild-type mice but not in beta-catenin-knockout littermates. In human proteinuric kidney diseases such as diabetic nephropathy and focal segmental glomerulosclerosis, we observed upregulation of Wnt1 and active beta-catenin in podocytes. Ectopic expression of either Wnt1 or stabilized beta-catenin in vitro induced the transcription factor Snail and suppressed nephrin expression, leading to podocyte dysfunction. These results suggest that targeting hyperactive Wnt/beta-catenin signaling may represent a novel therapeutic strategy for proteinuric kidney diseases.
                Bookmark

                Author and article information

                Journal
                Exp Ther Med
                Exp Ther Med
                ETM
                Experimental and Therapeutic Medicine
                D.A. Spandidos
                1792-0981
                1792-1015
                December 2016
                12 October 2016
                12 October 2016
                : 12
                : 6
                : 3515-3520
                Affiliations
                Department of Nephrology, Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan, Hubei 430061, P.R. China
                Author notes
                Correspondence to: Dr Xin-Rong Zou, Department of Nephrology, Hubei Provincial Hospital of Traditional Chinese Medicine, 4 Huanyuan Mountain, Wuhan, Hubei 430061, P.R. China, E-mail: xin_rongzou1@ 123456163.com
                Article
                ETM-0-0-3800
                10.3892/etm.2016.3800
                5228428
                28105085
                5805c05a-06bd-4a30-b48d-f520eca7070c
                Copyright: © Zou et al.

                This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

                History
                : 08 March 2016
                : 26 July 2016
                Categories
                Articles

                Medicine
                shen'an granules,diabetic nephropathy,wnt1,β-catenin
                Medicine
                shen'an granules, diabetic nephropathy, wnt1, β-catenin

                Comments

                Comment on this article