Role of connective tissue growth factor in profibrotic action of transforming growth factor-β:: A potential target for preventing renal fibrosis

被引：142

作者：

Yokoi, H ^{[1
]}

Sugawara, A ^{[1
]}

Mukoyama, M ^{[1
]}

Mori, K ^{[1
]}

Makino, H ^{[1
]}

Suganami, T ^{[1
]}

Nagae, T ^{[1
]}

Yahata, K ^{[1
]}

Fujinaga, Y ^{[1
]}

Tanaka, I ^{[1
]}

Nakao, K ^{[1
]}

机构：

[1] Kyoto Univ, Grad Sch Med, Dept Med & Clin Sci, Sakyo Ku, Kyoto 6068507, Japan

来源：

AMERICAN JOURNAL OF KIDNEY DISEASES | 2001年 / 38卷 / 04期

关键词：

connective tissue growth factor (CTGF); transforming growth factor-beta (TGF-beta); extracellular matrix (ECM); antisense oligonucleotide; obstructive nephropathy;

D O I：

10.1053/ajkd.2001.27422

中图分类号：

R5 [内科学]; R69 [泌尿科学（泌尿生殖系疾病）];

学科分类号：

1002 ; 100201 ;

摘要：

Tubulointerstitial fibrosis is a crucial process determining the progression and prognosis of various renal diseases. Connective tissue growth factor (CTGF), a novel fibrogenic protein Induced by transforming growth factor-beta (TGF-beta), is upregulated In various clinical and experimental nephropathies, but the significance of CTGF In the profibrotic action of TGF-beta is still poorly defined. To explore the implication of CTGF in renal fibrosis, we investigated gene expression of CTGF, fibronectin, and alpha1(l) collagen In an obstructive nephropathy model in rats. Furthermore, to elucidate the role of CTGF in TGF-beta -stimulated extracellular matrix accumulation, we analyzed the effects of blockade of endogenous CTGF using antisense oligodeoxynucleotides (ODNs) In cultured rat renal fibroblasts. After unilateral ureteral obstruction, TGF-beta1 and CTGF messenger RNA (mRNA) expression In the obstructed kidney was coordinately upregulated from the early stage of interstitial fibrosis, followed by marked Induction of fibronectin and alpha1(l) collagen mRNA expression. In cultured normal rat kidney fibroblast (NRK-49F) cells, CTGF antisense ODN transfection significantly attenuated TGF-beta1-induced fibronectin and alpha1(l) collagen mRNA expression compared with control reverse ODNs. These results indicate that CTGF has a crucial role in the profibrotic action of TGF-beta In renal fibroblasts, providing a potential therapeutic target against tubulointerstitial fibrosis. (C) 2001 by the National Kidney Foundation, Inc.

引用

页码：S134 / S138

页数：5

共 19 条

[1] TGF-beta in kidney fibrosis: A target for gene therapy [J].