title: Overexpression of connective tissue growth factor in podocytes worsens diabetic nephropathy in mice.
abstract: Connective tissue growth factor (CTGF) is a potent inducer of extracellular matrix accumulation. In diabetic nephropathy, CTGF expression is markedly upregulated both in podocytes and mesangial cells, and this may play an important role in its pathogenesis. We established podocyte-specific CTGF-transgenic mice, which were indistinguishable at baseline from their wild-type littermates. Twelve weeks after streptozotocin-induced diabetes, these transgenic mice showed a more severe proteinuria, mesangial expansion, and a decrease in matrix metalloproteinase-2 activity compared to diabetic wild-type mice. Furthermore, diabetic transgenic mice exhibited less podocin expression and a decreased number of diffusely vacuolated podocytes compared to diabetic wild-type mice. Importantly, induction of diabetes in CTGF-transgenic mice resulted in a further elevation of endogenous CTGF mRNA expression and protein in the glomerular mesangium. Our findings suggest that overexpression of CTGF in podocytes is sufficient to exacerbate proteinuria and mesangial expansion through a functional impairment and loss of podocytes.
authors: Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors: H
authors: H
authors: Yokoi
authors: M
authors: M
authors: Mukoyama
authors: K
authors: K
authors: Mori
authors: M
authors: M
authors: Kasahara
authors: T
authors: T
authors: Suganami
authors: K
authors: K
authors: Sawai
authors: T
authors: T
authors: Yoshioka
authors: Y
authors: Y
authors: Saito
authors: Y
authors: Y
authors: Ogawa
authors: T
authors: T
authors: Kuwabara
authors: A
authors: A
authors: Sugawara
authors: K
authors: K
authors: Nakao
mesh_terms: D000818:Animals; D055513:Connective Tissue Growth Factor; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000150:complications; D003928:Diabetic Nephropathies / Q000209:etiology* / Q000235:genetics / Q000473:pathology*; D005109:Extracellular Matrix / Q000378:metabolism; D015870:Gene Expression; D005920:Glomerular Mesangium / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D017874:Immediate-Early Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D050199:Podocytes / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology*; D011507:Proteinuria / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D011817:Rabbits
chemical_list: C526317:CCN2 protein, human; C526318:CCN2 protein, mouse; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D055513:Connective Tissue Growth Factor; D020778:Matrix Metalloproteinase 2