RGD Reference Report - Poly(ADP-ribose) polymerase 1 is indispensable for transforming growth factor-beta Induced Smad3 activation in vascular smooth muscle cell. - Rat Genome Database

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Poly(ADP-ribose) polymerase 1 is indispensable for transforming growth factor-beta Induced Smad3 activation in vascular smooth muscle cell.

Authors: Huang, D  Wang, Y  Wang, L  Zhang, F  Deng, S  Wang, R  Zhang, Y  Huang, K 
Citation: Huang D, etal., PLoS One. 2011;6(10):e27123. doi: 10.1371/journal.pone.0027123. Epub 2011 Oct 31.
RGD ID: 8554355
Pubmed: PMID:22073128   (View Abstract at PubMed)
PMCID: PMC3205050   (View Article at PubMed Central)
DOI: DOI:10.1371/journal.pone.0027123   (Journal Full-text)

BACKGROUND: Transforming growth factor type-beta (TGF-beta)/Smad pathway plays an essential role in vascular fibrosis. Reactive oxygen species (ROS) generation also mediates TGF-beta signaling-induced vascular fibrosis, suggesting that some sort of interaction exists between Smad and redox pathways. However, the underlying molecular mechanism is largely unknown. This study aims to investigate the influence of poly(ADP-ribose) polymerase 1 (PARP1), a downstream effector of ROS, on TGF-beta signaling transduction through Smad3 pathway in rat vascular smooth muscle cells (VSMCs). METHODS AND RESULTS: TGF-beta1 treatment promoted PARP1 activation through induction of ROS generation in rat VSMCs. TGF-beta1-induced phosphorylation and nuclear accumulation of Smad3 was prevented by treatment of cells with PARP inhibitor, 3-aminobenzamide (3AB) or N-(6-oxo-5,6-dihydrophenanthridin-2-yl)-2-(N,N-dimethylamino)acetami (PJ34), or PARP1 siRNA. TGF-beta1 treatment promoted poly(ADP-ribosy)lation of Smad3 via activation of PARP1 in the nucleus. Poly(ADP-ribosy)lation enhanced Smad-Smad binding element (SBE) complex formation in nuclear extracts and increased DNA binding activity of Smad3. Pretreatment with 3AB, PJ34, or PARP1 siRNA prevented TGF-beta1-induced Smad3 transactivation and expression of Smad3 target genes, including collagen Ialpha1, collagen IIIalpha1 and tissue inhibitor of metalloproteinase 1, in rat VSMCs. CONCLUSIONS: PARP1 is indispensable for TGF-beta1 induced Smad3 activation in rat VSMCs. Targeting PARP1 may be a promising therapeutic approach against vascular diseases induced by dysregulation of TGF-beta/Smad3 pathway.

Gene Ontology Annotations    Click to see Annotation Detail View

Cellular Component
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
nucleus located_inIDA 8554355; 8554355PMID:22073128BHF-UCL 

Molecular Function

Objects Annotated

Genes (Rattus norvegicus)
Parp1  (poly (ADP-ribose) polymerase 1)
Smad2  (SMAD family member 2)
Smad3  (SMAD family member 3)


Additional Information