Linked Life Data

11796725

Source:http://linkedlifedata.com/resource/pubmed/id/11796725

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
13
pubmed:dateCreated
2002-3-25
pubmed:abstractText
The activated hepatic stellate cell (HSC) is central to liver fibrosis as the major source of collagens I and III and the tissue inhibitors of metalloproteinase-1 (TIMP-1). During spontaneous recovery from liver fibrosis, there is a decrease of TIMP expression, an increase in collagenase activity, and increased apoptosis of HSC, highlighting a potential role for TIMP-1 in HSC survival. In this report, we use tissue culture and in vivo models to demonstrate that TIMP-1 directly inhibits HSC apoptosis. TIMP-1 demonstrated a consistent, significant, and dose-dependent antiapoptotic effect for HSC activated in tissue culture and stimulated to undergo apoptosis by serum deprivation, cycloheximide exposure, and nerve growth factor stimulation. A nonfunctional mutated TIMP-1 (T2G mutant) in which all other domains are conserved did not inhibit apoptosis, indicating that inhibition of apoptosis was mediated through MMP inhibition. Synthetic MMP inhibitors also inhibited HSC apoptosis. Studies of experimental liver cirrhosis demonstrated that persistent expression of TIMP-1 mRNA determined by PCR correlated with persistence of activated HSC quantified by alpha smooth muscle actin staining, while in fibrosis, loss of activated HSC correlated with a reduction in TIMP-1 mRNA. We conclude that TIMP-1 inhibits apoptosis of activated HSC via MMP inhibition.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
29
pubmed:volume
277
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
11069-76
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
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.
pubmed:affiliation
Liver Group, Division of Infection, Inflammation and Repair, University of Southampton, Hampshire SO16 6YD, United Kingdom. frm105@hotmail.com
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't