title: Protection of CTGF Antibody Against Diabetic Nephropathy in Mice Via Reducing Glomerular β-Catenin Expression and Podocyte Epithelial-Mesenchymal Transition.
abstract: Despite substantial progress in medical care, the morbidity rate of diabetic nephropathy (DN) remains high in patients with diabetes. Evidence suggests that connective tissue growth factor (CTGF) induced podocyte injury may contribute to DN and CTGF inhibition could reduce albuminuria. However, to date the mechanisms involved in the effect of CTGF on podocyte injury have not been fully understood. The aim of this study is to investigate the effects of therapeutic CTGF antibody on glomerular β-catenin expression and podocyte epithelial-mesenchymal transition (EMT) in diabetic mice. C57BL/6J mice were randomly divided into three groups as the following: the control, DN, and DN treated by CTGF antibody group. DN was induced by a single intraperitoneal injection of streptozotocin and then CTGF antibody was administrated three times per week for 8 weeks. Urinary albumin excretion, mesangial proliferation and matrix deposition, and β-catenin expression in glomeruli at mRNA and protein level were all increased in DN mice compared to that in the control. Besides, the development of EMT in podocytes from diabetic mice, demonstrated by the downregulation of nephrin and upregulation of desmin in glomeruli, was detected. Furthermore, blocking CTGF by specific antibody reduced albuminuria, prevented the overexpression of CTGF, as well as β-catenin, in glomeruli and subsequently ameliorated podocyte EMT in DN mice. In summary, this study suggested that CTGF antibody protected podocytes against injury in DN mice by reducing β-catenin overexpression and preventing podocyte EMT, which might provide new insight into the mechanism of CTGF inhibition in the treatment of DN. J. Cell. Biochem. 118: 3706-3712, 2017. © 2017 Wiley Periodicals, Inc.
authors.affiliation: Department of Nephrology, Affiliated Hospital of Nantong University, Nantong 226001, China.
authors.forename: Hou-Yong
authors.identifier: 0000-0001-7736-7108
authors.initials: HY
authors.lastname: Dai
authors.affiliation: Department of Nephrology, Affiliated Hospital of Nantong University, Nantong 226001, China.
authors.forename: Li-Na
authors.initials: LN
authors.lastname: Ma
authors.affiliation: Department of Nephrology, Affiliated Hospital of Nantong University, Nantong 226001, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Department of Nephrology, Affiliated Hospital of Nantong University, Nantong 226001, China.
authors.forename: Xiao-Lan
authors.initials: XL
authors.lastname: Chen
authors.affiliation: Department of Nephrology, Affiliated Hospital of Nantong University, Nantong 226001, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Shi
authors.affiliation: Department of Nephrology, Affiliated Hospital of Nantong University, Nantong 226001, China.
authors.forename: Ya-Ping
authors.initials: YP
authors.lastname: Fan
authors.affiliation: Department of Nephrology, Affiliated Hospital of Nantong University, Nantong 226001, China.|Department of Infection, Immunity and Inflammation, University of Leicester, University Hospitals of Leicester, Leicester, UK.
authors.forename: Bin
authors.initials: B
authors.lastname: Yang
mesh_terms: D000818:Animals; D000906:Antibodies / Q000494:pharmacology*; D055513:Connective Tissue Growth Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism; D003928:Diabetic Nephropathies / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D058750:Epithelial-Mesenchymal Transition; D007678:Kidney Glomerulus / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D050199:Podocytes / Q000378:metabolism* / Q000473:pathology; D051176:beta Catenin / Q000096:biosynthesis*
chemical_list: D000906:Antibodies; C526318:CCN2 protein, mouse; D051176:beta Catenin; D055513:Connective Tissue Growth Factor
keywords: CONNECTIVE TISSUE GROWTH FACTOR; DIABETIC NEPHROPATHY; EPITHELIAL-MESENCHYMAL TRANSITION; PODOCYTE; β-CATENIN