Linked Life Data

21402709

Source:http://linkedlifedata.com/resource/pubmed/id/21402709

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
17
pubmed:dateCreated
2011-4-25
pubmed:abstractText
Both TGF-? and myocardin (MYOCD) are important for smooth muscle cell (SMC) differentiation, but their precise role in regulating the initiation of SMC development is less clear. In TGF-?-induced SMC differentiation of pluripotent C3H10T1/2 progenitors, we found that TGF-? did not significantly induce Myocd mRNA expression until 18 h of stimulation. On the other hand, early SMC markers such as SM ?-actin, SM22?, and SM calponin were detectable beginning 2 or 4 h after TGF-? treatment. These results suggest that Myocd expression is blocked during the initiation of TGF-?-induced SMC differentiation. Consistent with its endogenous expression, Myocd promoter activity was not elevated until 18 h following TGF-? stimulation. Surprisingly, Smad signaling was inhibitory to Myocd expression because blockade of Smad signaling enhanced Myocd promoter activity. Overexpression of Smad3, but not Smad2, inhibited Myocd promoter activity. Conversely, shRNA knockdown of Smad3 allowed TGF-? to activate the Myocd promoter in the initial phase of induction. Myocd was activated by PI3 kinase signaling and its downstream target Nkx2.5. Interestingly, Smad3 did not affect PI3 kinase activity. However, Smad3 physically interacted with Nkx2.5. This interaction blocked Nkx2.5 binding to the Myocd promoter in the early stage of TGF-? induction, leading to inhibition of Myocd mRNA expression. Moreover, Smad3 inhibited Nkx2.5-activated Myocd promoter activity in a dose-dependent manner. Taken together, our results reveal a novel mechanism for Smad3-mediated inhibition of Myocd in the initiation phase of SMC differentiation.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1083-351X
pubmed:author
pubmed:issnType
Electronic
pubmed:day
29
pubmed:volume
286
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
15050-7
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Smad3-mediated myocardin silencing: a novel mechanism governing the initiation of smooth muscle differentiation.
pubmed:affiliation
Department of Physiology and Pharmacology, University of Georgia, Athens, Georgia 30602, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural