Linked Life Data

19837676

Source:http://linkedlifedata.com/resource/pubmed/id/19837676

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
51
pubmed:dateCreated
2009-12-16
pubmed:abstractText
Abnormal transforming growth factor-beta (TGF-beta) signaling is a critical contributor to the pathogenesis of various human diseases ranging from tissue fibrosis to tumor formation. Excessive TGF-beta signaling stimulates fibrotic responses. Recent research has focused in the main on the antiproliferative effects of TGF-beta in fibroblasts, and it is presently understood that TGF-beta-stimulated cyclooxygenase-2 (COX-2) induction in fibroblasts is essential for antifibroproliferative effects of TGF-beta. Both TGF-beta and COX-2 have been implicated in tumor growth, invasion, and metastasis, and therefore tumor-associated fibroblasts are a recent topic of interest. Here we report the identification of positive and negative regulatory factors of COX-2 expression induced by TGF-beta as determined using proteomic approaches. We show that TGF-beta coordinately up-regulates three factors, heterogeneous nuclear ribonucleoprotein A/B (HNRPAB), nucleotide diphosphate kinase A (NDPK A), and nucleotide diphosphate kinase A (NDPK B). Functional pathway analysis showed that HNRPAB augments mRNA and protein levels of COX-2 and subsequent prostaglandin E(2) (PGE(2)) production by suppressing degradation of COX-2 mRNA. In contrast, NDPK A and NDPK B attenuated mRNA and protein levels of COX-2 by affecting TGF-beta-Smad2/3/4 signaling at the receptor level. Collectively, we report on a new regulatory pathway of TGF-beta in controlling expression of COX-2 in fibroblasts, which advances our understanding of pathophysiological mechanisms of TGF-beta.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Cyclooxygenase 2, http://linkedlifedata.com/resource/pubmed/chemical/Dinoprostone, http://linkedlifedata.com/resource/pubmed/chemical/Heterogeneous-Nuclear..., http://linkedlifedata.com/resource/pubmed/chemical/Hnrpab protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/NM23 Nucleoside Diphosphate Kinases, http://linkedlifedata.com/resource/pubmed/chemical/Nme1 protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Ptgs2 protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger, http://linkedlifedata.com/resource/pubmed/chemical/Repressor Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Smad Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Transforming Growth Factor beta1
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1083-351X
pubmed:author
pubmed:issnType
Electronic
pubmed:day
18
pubmed:volume
284
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
35861-71
pubmed:dateRevised
2010-12-21
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Regulation of transforming growth factor-beta-dependent cyclooxygenase-2 expression in fibroblasts.
pubmed:affiliation
Departments of Cardiovascular Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't