Protection of CTGF Antibody Against Diabetic Nephropathy in Mice Via Reducing Glomerular β‐Catenin Expression and Podocyte Epithelial‐Mesenchymal Transition

• Published in: Journal of cellular biochemistry 2017-11, Vol.118 (11), p.3706-3712
• Main Authors: Dai, Hou‐Yong, Ma, Li‐Na, Cao, Yun, Chen, Xiao‐Lan, Shi, Hui, Fan, Ya‐Ping, Yang, Bin
• Format: Article
• Language: English
• Subjects: Albumin; Animals; Antibodies - pharmacology; beta Catenin - biosynthesis; Catenin; CONNECTIVE TISSUE GROWTH FACTOR; Connective Tissue Growth Factor - antagonists & inhibitors; Connective Tissue Growth Factor - metabolism; Connective tissues; Desmin; Diabetes; Diabetes mellitus; Diabetic Nephropathies - metabolism; Diabetic Nephropathies - pathology; Diabetic Nephropathies - prevention & control; DIABETIC NEPHROPATHY; EPITHELIAL‐MESENCHYMAL TRANSITION; Excretion; Gene expression; Inhibition; Injury prevention; Kidney Glomerulus - metabolism; Kidney Glomerulus - pathology; Male; Mesenchyme; Mice; Morbidity; mRNA; Nephropathy; PODOCYTE; Podocytes - metabolism; Podocytes - pathology; Rodents; Streptozocin; β‐CATENIN
• ISSN: 0730-2312; 1097-4644
• DOI: 10.1002/jcb.26017

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. CTGF antibody protected podocytes against injury in DN mice by reducing β‐catenin overexpression and preventing podocyte EMT.