title: CTGF mediates high-glucose induced epithelial-mesenchymal transition through activation of β-catenin in podocytes.
abstract: OBJECTIVE
  It is known that connective tissue growth factor (CTGF) and β-catenin are involved in DN; however, the underlying molecular mechanisms remain unknown. Here we hypothesized that podocytes undergo epithelial-mesenchymal transition (EMT) in high-glucose condition and CTGF mediates high-glucose induced EMT by activating β-catenin in podocytes.
  
  
  METHODS
  The differentiated podocytes were cultured and divided into three groups: the normal glucose group (5 mmol/L glucose), the high-glucose group (30 mmol/L glucose), and the osmotic control group (5 mmol/L glucose supplemented with 25 mmol/L mannitol). The morphology of cultured podocytes was observed under phase contrast microscopy. To study the relevant markers of EMT, as well as CTGF and β-catenin, the mRNA and protein expressions were analyzed by real-time PCR and western blotting, respectively. In addition, the effects of inhibition CTGF by anti-CTGF antibody on high-glucose-induced EMT and β-catenin expression in podocytes were studied.
  
  
  RESULTS
  High glucose not only induced phenotypic transition of podocytes but also increased the expression of CTGF and β-catenin. Under high-glucose condition, podocytes underwent EMT, which were demonstrated by downregulation of nephrin and upregulation of desmin. Moreover, high-glucose-induced EMT and β-catenin overexpression in podocytes were attenuated by anti-CTGF antibody.
  
  
  CONCLUSIONS
  CTGF and β-catenin are involved in the EMT of podocytes in diabetes. CTGF mediates high-glucose induced EMT through activation of β-catenin in podocytes. CTGF inhibition may protect podocytes from EMT in diabetes.
authors.affiliation: a Department of Nephrology , Affiliated Hospital of Nantong University , Nantong , China.
authors.forename: Houyong
authors.initials: H
authors.lastname: Dai
authors.affiliation: a Department of Nephrology , Affiliated Hospital of Nantong University , Nantong , China.
authors.forename: Yide
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: a Department of Nephrology , Affiliated Hospital of Nantong University , Nantong , China.
authors.forename: Li
authors.initials: L
authors.lastname: Yuan
authors.affiliation: a Department of Nephrology , Affiliated Hospital of Nantong University , Nantong , China.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Wu
authors.affiliation: a Department of Nephrology , Affiliated Hospital of Nantong University , Nantong , China.
authors.forename: Lina
authors.initials: L
authors.lastname: Ma
authors.affiliation: a Department of Nephrology , Affiliated Hospital of Nantong University , Nantong , China.
authors.forename: Hui
authors.initials: H
authors.lastname: Shi
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D055513:Connective Tissue Growth Factor / Q000235:genetics / Q000378:metabolism*; D058750:Epithelial-Mesenchymal Transition; D005947:Glucose / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D050199:Podocytes / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
chemical_list: C526318:CCN2 protein, mouse; C495267:CTNNB1 protein, mouse; D008565:Membrane Proteins; D034741:RNA, Small Interfering; D051176:beta Catenin; C113267:nephrin; D055513:Connective Tissue Growth Factor; D005947:Glucose
keywords: CTGF; diabetes; epithelial–mesenchymal transition; podocyte; β-Catenin