Matrix metalloproteinases, the pros and cons, in liver fibrosis - PubMed (original) (raw)

Review

Matrix metalloproteinases, the pros and cons, in liver fibrosis

Yuan-Ping Han. J Gastroenterol Hepatol. 2006 Oct.

Abstract

Residing in the space of Disse within loose extracellular matrix (ECM) resembling that in basement membranes, the hepatic stellate cells (HSC) remain in quiescence as vitamin A storage cells. In response to liver injury HSC undergo morphologic and functional trans-differentiation, converting from vitamin A-storing, star-like cells into contractile myofibroblastic cells, a process called activation. Accompanying cellular activation, the ECM components in the space of Disse switch from matrices rich in type-IV collagen and laminin, into condensed interstitial ECM, indicating that proteolytic degradation may occur to change the microenvironment in sinusoids as well as the fate of HSC. Indeed, matrix metalloproteinases (MMP), a family of ECM degradative enzymes, are promptly expressed by HSC in response to diverse hepatic toxins. In vitro experiments also demonstrated the role of MMP in activation of HSC cultured in 3-D ECM. Conversely, MMP may also contribute to regression of liver fibrosis through cleavage of the fibrillar ECM and promotion of apoptosis among the activated HSC. Thus, MMP play dual roles both bad and good in liver fibrosis, depending on the timing.

PubMed Disclaimer

Figures

Figure 1

Figure 1

Timeline of events during activation of hepatic stellate cells (HSC) and fibrogenesis in an animal model. In response to injury pro-inflammatory cytokines are promptly increased in wound areas, which induce matrix metalloproteinase (MMP) expression by hepatic cells including HSC. The MMP secreted by HSC degrade the normal extracellular matrix (ECM) in the space of Disse. This cytokine-induced ECM degradation leads to activation of HSC. Consequently, a population of the HSC undergo apoptosis while others trans-differentiate into myofibroblasts that produce fibrillar ECM.

Similar articles

Cited by

References

    1. Parks WC. Matrix metalloproteinases in repair. Wound Repair Regen. 1999;7:423–32. - PubMed
    1. Birkedal-Hansen H. Proteolytic remodeling of extracellular matrix. Curr Opin Cell Biol. 1995;7:728–35. - PubMed
    1. Werb Z, Chin JR. Extracellular matrix remodeling during morphogenesis. Ann NY Acad Sci. 1998;857:110–18. - PubMed
    1. Nagase H, Woessner JF., Jr The matrix metalloproteinases and their inhibitors. J Biol Chem. 1999;274(21):491–4. - PubMed
    1. Murphy G, Docherty AJ. The matrix metalloproteinases and their inhibitors. Am J Respir Cell Mol Biol. 1992;7:120–5. - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources