Location of Repository

N-Cadherin cleavage during activated hepatic stellate cell apoptosis is inhibited by tissue inhibitor of metalloproteinase-1. [In supplement: 11th International Symposium on the Cells of the Hepatic Sinusoid and their Relation to Other Cells]

By Frank Murphy, Julian Waung, Jane Collins, Michael J.P. Arthur, Hideaki Nagase, Derek Mann, R. Christopher Benyon and John P. Iredale

Abstract

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

Topics: RM, QP, QH301
Year: 2004
OAI identifier: oai:eprints.soton.ac.uk:8191
Provided by: e-Prints Soton

Suggested articles

Preview

Citations

  1. (1989). DM: Lipocytes from normal rat liver release a neutral metalloproteinase that degrades basement membrane (type IV) collagen. doi
  2. (2001). Iredale JP: Apoptosis of hepatic stellate cells: involvement in resolution of biliary fibrosis and regulation by soluble growth factors. Gut doi
  3. (2002). Iredale JP: 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. doi
  4. (1998). MJP: Mechanisms of spontaneous resolution of rat liver fibrosis: hepatic stellate cell apoptosis and reduced hepatic expression of metalloproteinase inhibitors. doi
  5. (2001). MMP inhibitors augment fibroblast adhesion through stabilization of focal adhesion contacts and up-regulation of cadherin function. doi
  6. (2001). N-cadherin-mediated intercellular interactions promote survival and migration of melanoma cells. Cancer Res
  7. (1993). The cellular basis of hepatic fibrosis: Mechanisms and treatment strategies. doi

To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.