Linked Life Data

16871591

Source:http://linkedlifedata.com/resource/pubmed/id/16871591

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2006-8-2
pubmed:abstractText
Cholestasis occurs in a variety of clinical settings and often results in liver injury and secondary biliary fibrosis. Several matrix metalloproteinases (MMPs) are upregulated in the liver during cholestasis. The function of the major interstitial collagenase, MMP-13, in the initial phase of liver fibrosis is unknown. The aim of this study was to evaluate the role of MMP-13 during the development of cholestasis-induced liver fibrosis by comparing wild-type and MMP-13-deficient mice. Cholestasis was induced by bile duct ligation (BDL) for 5 days or 3 weeks. Activation and proliferation of hepatic stellate cells (HSCs) were detected by immunohistochemistry. Expression of MMP-13 mRNA increased significantly in BDL livers of WT mice. After BDL for 3 weeks liver fibrosis was suppressed in MMP-13-deficient mice versus WT animals. Activation and proliferation of HSCs were also suppressed in livers of MMP-13-deficient mice after BDL. To clarify the mechanism of this suppression, samples from 5-day BDL mice were used for evaluation of liver injury. Compared with those in WT animals, serum ALT and the number of hepatic neutrophils were reduced in MMP-13-deficient mice. Increased expression of the mRNA of inflammatory mediators such as tumor necrosis factor-alpha (TNF-alpha) was significantly suppressed in livers of MMP-13-deficient mice. Upregulation of fibrogenic markers, for example, transforming growth factor beta1 (TGF-beta1), was also significantly suppressed in livers of MMP-13-deficient mice versus in WT mice. In conclusion, distinct from the known function of interstitial collagenase to reduce liver fibrosis by degrading the extracellular matrix, MMP-13 contributes to accelerating fibrogenesis in cholestatic livers by mediating the initial inflammation of the liver.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0270-9139
pubmed:author
pubmed:issnType
Print
pubmed:volume
44
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
420-9
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
Loss of MMP 13 attenuates murine hepatic injury and fibrosis during cholestasis.
pubmed:affiliation
Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, N.I.H., Extramural