Linked Life Data

17272676

Source:http://linkedlifedata.com/resource/pubmed/id/17272676

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2007-4-17
pubmed:abstractText
The immunosuppressive drug mycophenolate mofetil (MMF) is used to prevent organ rejection after transplantation and has shown some efficacy to prevent the fibrotic complications that occur during autoimmune diseases such as systemic sclerosis or during graft-versus-host disease (GVHD). We tested the hypothesis that MMF may exert direct effects on fibroblast extracellular matrix remodeling. Incubation of human lung fibroblast cultures with MMF led to dose- and time-dependent reduction in the synthesis and expression of type I collagen. Inhibition of COL1A1 and COL1A2 mRNA steady-state levels occurred at the level of transcription via repression of their promoters. In contrast, MMF significantly enhanced the expression and the synthesis of interstitial collagenase (matrix metalloproteinase-1). MMF was also found to diminish the capacity of fibroblast to contract mechanically unloaded collagen lattices and to reduce the synthesis of alpha-smooth muscle actin, a marker of the contractile myofibroblast phenotype. In addition, MMF diminished the fibroblasts motility. In conclusion, we provide novel mechanism by which MMF alters fibroblast functions important for wound healing and implicated in the development of tissue fibrosis, e.g., collagen production, extracellular matrix contraction, and cell migration. Such properties may contribute to the beneficial therapeutic effects of MMF against fibrotic lesions developing in systemic sclerosis or during GVHD.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0022-3565
pubmed:author
pubmed:issnType
Print
pubmed:volume
321
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
583-9
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
In vitro evidence for a direct antifibrotic role of the immunosuppressive drug mycophenolate mofetil.
pubmed:affiliation
Institut National de la Santé et de la Recherche Médicale U697, Hôpital Saint-Louis, Pavillon Bazin, 1 Avenue Claude Vellefaux, 75010 Paris, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't