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

  • Authors:
    • Kazuhiro Kotoh
    • Makoto Nakamuta
    • Motoyuki Kohjima
    • Marie Fukushima
    • Shusuke Morizono
    • Naoya Kobayashi
    • Munechika Enjoji
    • Hajime Nawata
  • View Affiliations

  • Published online on: December 1, 2004     https://doi.org/10.3892/ijmm.14.6.1049
  • Pages: 1049-1053
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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 α5β1 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 μg/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.

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December 2004
Volume 14 Issue 6

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Kotoh K, Nakamuta M, Kohjima M, Fukushima M, Morizono S, Kobayashi N, Enjoji M and Nawata H: Arg-Gly-Asp (RGD) peptide ameliorates carbon tetrachloride-induced liver fibrosis via inhibition of collagen production and acceleration of collagenase activity. Int J Mol Med 14: 1049-1053, 2004
APA
Kotoh, K., Nakamuta, M., Kohjima, M., Fukushima, M., Morizono, S., Kobayashi, N. ... Nawata, H. (2004). Arg-Gly-Asp (RGD) peptide ameliorates carbon tetrachloride-induced liver fibrosis via inhibition of collagen production and acceleration of collagenase activity. International Journal of Molecular Medicine, 14, 1049-1053. https://doi.org/10.3892/ijmm.14.6.1049
MLA
Kotoh, K., Nakamuta, M., Kohjima, M., Fukushima, M., Morizono, S., Kobayashi, N., Enjoji, M., Nawata, H."Arg-Gly-Asp (RGD) peptide ameliorates carbon tetrachloride-induced liver fibrosis via inhibition of collagen production and acceleration of collagenase activity". International Journal of Molecular Medicine 14.6 (2004): 1049-1053.
Chicago
Kotoh, K., Nakamuta, M., Kohjima, M., Fukushima, M., Morizono, S., Kobayashi, N., Enjoji, M., Nawata, H."Arg-Gly-Asp (RGD) peptide ameliorates carbon tetrachloride-induced liver fibrosis via inhibition of collagen production and acceleration of collagenase activity". International Journal of Molecular Medicine 14, no. 6 (2004): 1049-1053. https://doi.org/10.3892/ijmm.14.6.1049