N-Cadherin cleavage during activated hepatic stell...[Comp Hepatol. 2004]

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1: Comp Hepatol. 2004 Jan 14;3 Suppl 1:S8. Links

N-Cadherin cleavage during activated hepatic stellate cell apoptosis is inhibited by tissue inhibitor of metalloproteinase-1.

Murphy F, Waung J, Collins J, Arthur MJ, Nagase H, Mann D, Benyon RC, Iredale JP.

Liver group, Division of Infection, Inflammation and Repair, Southampton University, Southampton General Hospital, Tremona Road, Southampton SO16 6YD, UK. frm105@hotmail.com

Apoptosis of hepatic stellate cells (HSC) has previously been shown to occur during spontaneous resolution of experimental liver fibrosis. TIMP-1 has also been shown to have a key role because of its ability to inhibit apoptosis of HSC via matrix metalloproteinase (MMP) inhibition. This has led to further study of novel substrates for MMPs that might impact on HSC survival. N-Cadherin is known to mediate cell-cell contacts in fibroblasts. In this study we demonstrate that N-Cadherin is expressed by activated rat HSC. Furthermore, during apoptosis of HSC, the N-Cadherin is cleaved into smaller fragments. Apoptosis of HSC may be inhibited by TIMP-1. This is associated with reduced fragmentation of N-Cadherin. N-Cadherin may have an important role in supporting HSC survival while N-Cadherin cleavage may play a part in promoting HSC apoptosis in recovery from liver fibrosis.

PMID: 14960160 [PubMed - as supplied by publisher]

PMCID: PMC2410231

Inhibition of apoptosis of activated hepatic stellate cells by tissue inhibitor of metalloproteinase-1 is mediated via effects on matrix metalloproteinase inhibition: implications for reversibility of liver fibrosis. [J Biol Chem. 2002]
ReviewTissue inhibitors of metalloproteinases, hepatic stellate cells and liver fibrosis. [J Gastroenterol Hepatol. 1998]
Mechanisms of spontaneous resolution of rat liver fibrosis. Hepatic stellate cell apoptosis and reduced hepatic expression of metalloproteinase inhibitors. [J Clin Invest. 1998]
Tissue inhibitor of metalloproteinases-1 attenuates spontaneous liver fibrosis resolution in the transgenic mouse. [Hepatology. 2002]
ReviewThe role and regulation of hepatic stellate cell apoptosis in reversal of liver fibrosis. [Apoptosis. 2005]

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N-Cadherin cleavage during activated hepatic stellate cell apoptosis is inhibited by tissue inhibitor of metalloproteinase-1.

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