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

Yokoi, Hideki; Sugawara, Akira; Mukoyama, Masashi; Mori, Kiyoshi; Makino, Hisashi; Suganami, Takayoshi; Nagae, Tetsuya; Yahata, Kensei; Fujinaga, Yuriko; Tanaka, Issei; Nakao, Kazuwa

doi:10.1053/ajkd.2001.27422

Cited by 142 publications

(107 citation statements)

References 17 publications

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“…Early studies described the functions of CTGF as connective tissue cell proliferation, differentiation, chemotaxis and adhesion [8,9,43]. CTGF is synthesised by fibroblasts and stimulates the proliferation and chemotaxis of these cells as well as the production of various ECM components in fibroblast cultures, including collagen I, fibronectin and collagen IV [44,45]. CTGF is produced at increased levels during normal wound repair [8] and at sites of fibrogenesis [11,45].…”

Section: Discussionmentioning

confidence: 99%

“…CTGF is synthesised by fibroblasts and stimulates the proliferation and chemotaxis of these cells as well as the production of various ECM components in fibroblast cultures, including collagen I, fibronectin and collagen IV [44,45]. CTGF is produced at increased levels during normal wound repair [8] and at sites of fibrogenesis [11,45]. CTGF is normally produced in keratinocytes in the epidermis [46], and in cell culture [47], so it may have a role in the remodelling of the epidermis after wounding.…”

Section: Discussionmentioning

confidence: 99%

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A novel primate model of delayed wound healing in diabetes: dysregulation of connective tissue growth factor

et al. 2009

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Aims/hypothesis Chronic non-healing wounds are a common complication of diabetes. Prolonged inflammation and decreased matrix accumulation may contribute. Connective tissue growth factor (CTGF) is induced during normal wound healing, but its regulation in diabetic wounds is unknown. We developed a primate model for the study of in vivo wound healing in baboons with long diabetes duration. Methods Drum implants were placed subcutaneously into thighs of diabetic and non-diabetic control baboons. After 2 and 4 weeks the skin incision sites were removed for measurement of breaking strength and epithelial thickness.Drum implants were removed for analysis of granulation tissue and inflammatory cells, CTGF and tissue inhibitor of matrix metalloproteinase (TIMP-1). Degradation of added CTGF by wound fluid was also examined. Results Healed incision site skin was stiffer (less elastic) in diabetic baboons and epithelial remodelling was slower compared with controls. Granulation tissue from diabetic baboons was reduced at 2 and 4 weeks, with increased vessel lumen areas at 4 weeks. Macrophages were reduced while neutrophils persisted in diabetic tissue. In diabetic wound tissue at 4 weeks there was less CTGF induced, as shown by immunohistochemistry, compared with controls. In contrast, Electronic supplementary material The online version of this article

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

A novel primate model of delayed wound healing in diabetes: dysregulation of connective tissue growth factor

et al. 2009

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“…Application of CTGF antisense ODNs into cultured renal fibroblasts attenuated TGF-β-induced fibronectin and collagen I mRNA expression [73]. Very recent preliminary results in rodents show reduction of collagen deposition after application of antibodies against CTGF in the unilateral ureter-ligated obstruction model and 5/6 nephrectomy-induced fibrosis [74].…”

Section: Connective Tissue Growth Factormentioning

confidence: 99%

ECM homeostasis in renal diseases: a genomic approach

Eikmans

Baelde

Heer

et al. 2003

The Journal of Pathology

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Chronic renal disease is in general histologically accompanied by a vast amount of scar tissue, ie glomerulosclerosis and interstitial fibrosis. Scarring results from excessive accumulation of extracellular matrix (ECM) components, a process driven by a plethora of cytokines and growth factors. Studies in experimental renal disease which target these regulators using gene therapy limit or prevent the development of scarring. This review focuses specifically on the role of transforming growth factor-beta, platelet-derived growth factor, connective tissue growth factor, hepatocyte growth factor, and epidermal growth factor. The results obtained in animal models hold promise for molecular intervention strategies in human renal disease. Microarray technology allows large-scale gene expression profiling in kidney tissue to identify common molecular pathways in a step towards discovery of new drug targets. Molecular techniques are expected to be used for diagnostic and prognostic purposes in nephrological practice to supplement renal biopsy. Several studies already show that molecular techniques might be of use in routine diagnostic practice. Improvement of diagnosis and prediction of outcome in renal patients might lead to more efficient and earlier therapeutic intervention.

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“…Upregulated expression of TGF-␤ has been observed in human and experimental models (13). Connective tissue growth factor, a novel profibrogenic factor, may be an important downstream mediator of TGF-␤ profibrotic activities (14,15). Basic fibroblast growth factor (FGF), a mitogenic factor for various types of renal cells, is upregulated in fibrotic kidneys (16) and mediates TGF-␤-induced cell proliferation in renal interstitial fibroblasts (17).…”

mentioning

confidence: 99%

Activin A Is a Potent Activator of Renal Interstitial Fibroblasts

Yamashita¹,

Maeshima

Kojima

et al. 2004

Journal of the American Society of Nephrology

130

110

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Abstract. The present study was conducted to examine the involvement of the activin-follistatin system in the fibrotic process of the kidney. Immunoreactive activin A was upregulated in tubular cells in the kidneys with unilateral ureteral obstruction but not in normal and contralateral kidneys. Activin A promoted cell proliferation, enhanced the expression of type I collagen mRNA, and induced the production of ␣-smooth muscle actin in a rat kidney fibroblast cell line (NRK-49F cells) as well as in primary cultured renal interstitial fibroblasts. In contrast, activin A did not affect the expressions of ␣-smooth muscle actin and type I collagen in renal epithelial tubular cell lines LLC-PK1, and MDCK. Follistatin, an antagonist of activin A, significantly inhibited cell proliferation in NRK-49F cells. Blockade of activin signaling by overexpression of truncated type II activin receptor, which lacked the intracellular kinase domain, decreased cell proliferation and reduced the expression level of type I collagen mRNA in NRK-49F cells. The expression of activin A was induced by TGF-␤1 or activin A itself. Induction of type I collagen expression by TGF-␤1 was reduced by follistatin or by overexpression of truncated type II activin receptor. These results suggest that activin A produced by tubular cells acts as a paracrine factor that activates renal interstitial fibroblasts during the fibrotic processes of the kidney.

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

Cited by 142 publications

References 17 publications

A novel primate model of delayed wound healing in diabetes: dysregulation of connective tissue growth factor

A novel primate model of delayed wound healing in diabetes: dysregulation of connective tissue growth factor

ECM homeostasis in renal diseases: a genomic approach

Activin A Is a Potent Activator of Renal Interstitial Fibroblasts

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