Arg-Gly-Asp (RGD) peptide ameliorates carbon tetrachloride-induced liver fibrosis via inhibition of collagen production and acceleration of collagenase activity.

Kazuhiro Kotoh, Makoto Nakamuta, Motoyuki Kohjima, Marie Fukushima, Shusuke Morizono, Naoya Kobayashi, Munechika Enjoji, Hajime Nawata

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Liver cirrhosis is caused by a relative imbalance between synthesis and degradation of collagens. Arg-Gly-Asp (RGD) peptide is a major adhesive domain of several extracellular matrix (ECM) components, such as that involved in the binding of fibronectin to the alpha5beta1 integrin receptor. We previously reported that RGD peptide increased the expression of matrix metalloproteinase in hepatic stellate cells (HSCs) which play a major role in hepatic fibrosis. We evaluated whether RGD-peptides inhibit the progression of liver fibrosis in an animal model of carbon tetrachloride-induced hepatotoxicity. RGD peptide (GRGDS) (1 mg/kg body weight) was injected intraperitoneally (i.p.) 3 times a week for one month. The group treated with control peptide (GRGES) showed pathologically typical hepatic fibrosis, while the RGD-treated group showed minimal fibrotic changes. The liver contents of collagen and hydroxyproline in the RGD-treated group was significantly lower than that of the control group. Collagenase activity measured in liver homogenates was significantly higher in the treated group than in the control group. In an in vitro study using TWNT-4 cells derived from human HSCs, RGD peptide (100 mug/ml) reduced the expression of type I collagen and tissue inhibitor of matrix metalloproteinase-1, and increased that of matrix metalloproteinase-1. These results indicated that RGD peptides inhibited liver fibrosis associated with both decreased collagen production and increased collagenase acitivity, and suggested that RGD peptide might be useful for the therapy of hepatic fibrosis.

Original languageEnglish
Pages (from-to)1049-1053
Number of pages5
JournalInternational journal of molecular medicine
Volume14
Issue number6
Publication statusPublished - Jan 1 2004

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Carbon Tetrachloride
Collagenases
Liver Cirrhosis
Collagen
Liver
Hepatic Stellate Cells
Matrix Metalloproteinase 1
Fibrosis
glycyl-arginyl-glycyl-glutamyl-serine
glycyl-arginyl-glycyl-aspartyl-serine
Integrin alpha5beta1
Control Groups
Tissue Inhibitor of Metalloproteinase-1
Hydroxyproline
Collagen Type I
arginyl-glycyl-aspartic acid
Matrix Metalloproteinases
Fibronectins
Adhesives
Extracellular Matrix

All Science Journal Classification (ASJC) codes

  • Genetics

Cite this

Arg-Gly-Asp (RGD) peptide ameliorates carbon tetrachloride-induced liver fibrosis via inhibition of collagen production and acceleration of collagenase activity. / Kotoh, Kazuhiro; Nakamuta, Makoto; Kohjima, Motoyuki; Fukushima, Marie; Morizono, Shusuke; Kobayashi, Naoya; Enjoji, Munechika; Nawata, Hajime.

In: International journal of molecular medicine, Vol. 14, No. 6, 01.01.2004, p. 1049-1053.

Research output: Contribution to journalArticle

Kotoh, Kazuhiro ; Nakamuta, Makoto ; Kohjima, Motoyuki ; Fukushima, Marie ; Morizono, Shusuke ; Kobayashi, Naoya ; Enjoji, Munechika ; Nawata, Hajime. / Arg-Gly-Asp (RGD) peptide ameliorates carbon tetrachloride-induced liver fibrosis via inhibition of collagen production and acceleration of collagenase activity. In: International journal of molecular medicine. 2004 ; Vol. 14, No. 6. pp. 1049-1053.
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