RGD Reference Report - Smad3 mediates transforming growth factor-beta-induced alpha-smooth muscle actin expression. - Rat Genome Database

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Smad3 mediates transforming growth factor-beta-induced alpha-smooth muscle actin expression.

Authors: Hu, B  Wu, Z  Phan, SH 
Citation: Hu B, etal., Am J Respir Cell Mol Biol 2003 Sep;29(3 Pt 1):397-404. Epub 2003 Apr 17.
RGD ID: 1299323
Pubmed: PMID:12702545   (View Abstract at PubMed)
DOI: DOI:10.1165/rcmb.2003-0063OC   (Journal Full-text)

Transforming growth factor-beta (TGF-beta)-induced alpha-smooth muscle actin (ASMA) expression is a key indicator of myofibroblast differentiation from fibroblasts. Recent studies suggest that a TGF-beta control element is important in the regulation of the ASMA gene promoter by TGF-beta. In this study, the role of Smad3, a key component of the Smad pathway that mediates TGF-beta signaling in regulation of ASMA gene expression, is investigated. All members of the Smad family were expressed in rat lung fibroblasts, and Smad3 expression was elevated upon TGF-beta 1 treatment. Transfection with a Smad3-expressing plasmid markedly increased Smad3 and ASMA protein expression, whereas transfection with an antisense Smad3 plasmid suppressed Smad3 and ASMA expression. Similar effects were noted when the cloned rat ASMA promoter-luciferase reporter gene construct was used to monitor transcriptional activation of the ASMA gene. Electrophoretic mobility shift assays and DNA affinity precipitation indicated Smad3 binding to at least two regions of the promoter containing CAGA motifs, termed Smad3-binding elements (SBEs). Mutation of one of the SBEs decreased promoter activity significantly, indicative of a functional role for this SBE. Taken together, these findings suggest a role for Smad3 in TGF-beta regulation of ASMA gene expression in myofibroblast differentiation.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
positive regulation of transcription by RNA polymerase II  IDA 1299323alpha-smooth muscle actin in lung fibroblastsRGD 

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
DNA-binding transcription factor activity  IDA 1299323 RGD 
sequence-specific DNA binding  IDA 1299323Smad binding elements SBE1 and SBE2 in alpha-smooth muscle actin promoterRGD 

Molecular Pathway Annotations    Click to see Annotation Detail View

RGD Manual Annotations

TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
transforming growth factor-beta Smad dependent signaling pathway   IDA 1299323 RGD 
Objects Annotated

Genes (Rattus norvegicus)
Smad3  (SMAD family member 3)

Objects referenced in this article
Gene TGFB1 transforming growth factor beta 1 Homo sapiens
Gene Tgfb1 transforming growth factor, beta 1 Mus musculus
Gene Acta2 actin alpha 2, smooth muscle Rattus norvegicus
Gene Tgfb1 transforming growth factor, beta 1 Rattus norvegicus

Additional Information