Linked Life Data

17556364

Source:http://linkedlifedata.com/resource/pubmed/id/17556364

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
31
pubmed:dateCreated
2007-7-30
pubmed:abstractText
Fibrocytes are a distinct population of fibroblast-like progenitor cells in peripheral blood that have recently been shown to possess plasticity to differentiate along mesenchymal lineages, including commitment to myofibroblast and adipocyte cells. Here, we demonstrated that transforming growth factor (TGF) beta1 drives fibrocyte-to-myofibroblast differentiation through activating Smad2/3 and SAPK/JNK MAPK pathways, which in turn stimulates alpha-smooth muscle actin expression. We determined that SAPK/JNK signaling acts in a positive feedback loop to modulate Smad2/3 nuclear availability and Smad2/3-dependent transcription. Conversely, fibrocyte-to-adipocyte differentiation is driven by the peroxisome proliferator-activated receptor (PPAR) gamma agonist troglitazone, which is associated with cytoplasmic lipid accumulation and induction of aP2. Treatment with troglitazone also disrupted TGF beta 1-activated SAPK/JNK signaling, leading to decreased Smad2/3 transactivation activity and alpha-smooth muscle actin expression. Interestingly, TGF beta 1 was demonstrated to have reciprocal inhibition on fibrocyte differentiation to adipocytes. By activating SAPK/JNK signaling, which is normally suppressed during adipogenesis, PPARgamma-dependent transactivation activity and induction of aP2 expression were disrupted. Taken together, within the context of the local microenvironmental niche, the delicate balance of PPARgamma and TGF beta 1 activation drives the selection of an adipocyte or myofibroblast differentiation pathway through SAPK/JNK signaling.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
3
pubmed:volume
282
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
22910-20
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Differentiation of human circulating fibrocytes as mediated by transforming growth factor-beta and peroxisome proliferator-activated receptor gamma.
pubmed:affiliation
Center for Human Nutrition and the Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, UCLA, Los Angeles, California 90024, USA.
pubmed:publicationType
Journal Article