| http://purl.uniprot.org/citations/24613410 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/24613410 | http://www.w3.org/2000/01/rdf-schema#comment | "Transforming growth factor-β1 (TGF-β1) regulates the tissue response to injury and is the principal driver of excessive scarring leading to fibrosis and eventual organ failure. The TGF-β1 effectors SMAD3 and p53 are major contributors to disease progression. While SMAD3 is an established pro-fibrotic factor, the role of p53 in the TGF-β1-induced fibrotic program is not clear. p53 gene silencing, genetic ablation/subsequent rescue, and pharmacological inhibition confirmed that p53 was required for expression of plasminogen activator inhibitor-1 (PAI-1), a major TGF-β1 target gene and a key causative element in fibrotic disorders. TGF-β1 regulated p53 activity by stimulating p53(Ser15 and 9) phosphorylation and acetylation, promoting interactions with activated SMADs and subsequent binding of p53/SMAD3 to the PAI-1 promoter in HK-2 human renal tubular epithelial cells and HaCaT human keratinocytes. Immunohistochemistry revealed prominent co-induction of SMAD3, p53 and PAI-1 in the tubular epithelium of the obstructed kidney consistent with a potential in vivo role for p53 and SMADs in TGF-β1-driven renal fibrosis. TGF-β1-initiated phosphorylation of p53(Ser15) and up-regulation of expression of several pro-fibrotic genes, moreover, was dependent on the rapid generation of reactive oxygen species (ROS). shRNA silencing of the p22(Phox) subunit of NADP(H) oxidases in HK-2 cells partially attenuated (over 50%) p53(Ser15) phosphorylation and PAI-1 induction. These studies highlight the role of free radicals in p53 activation and subsequent pro-fibrotic reprogramming by TGF-β1 via the SMAD3-p53 transcriptional axis. Present findings provide a rationale for therapeutic targeting of SMAD3-p53 in aberrant TGF-β1 signaling associated with renal fibrosis."xsd:string |
| http://purl.uniprot.org/citations/24613410 | http://purl.org/dc/terms/identifier | "doi:10.1016/j.cellsig.2014.02.017"xsd:string |
| http://purl.uniprot.org/citations/24613410 | http://purl.uniprot.org/core/author | "Higgins P.J."xsd:string |
| http://purl.uniprot.org/citations/24613410 | http://purl.uniprot.org/core/author | "Samarakoon R."xsd:string |
| http://purl.uniprot.org/citations/24613410 | http://purl.uniprot.org/core/author | "Meldrum K.K."xsd:string |
| http://purl.uniprot.org/citations/24613410 | http://purl.uniprot.org/core/author | "Overstreet J.M."xsd:string |
| http://purl.uniprot.org/citations/24613410 | http://purl.uniprot.org/core/date | "2014"xsd:gYear |
| http://purl.uniprot.org/citations/24613410 | http://purl.uniprot.org/core/name | "Cell Signal"xsd:string |
| http://purl.uniprot.org/citations/24613410 | http://purl.uniprot.org/core/pages | "1427-1436"xsd:string |
| http://purl.uniprot.org/citations/24613410 | http://purl.uniprot.org/core/title | "Redox control of p53 in the transcriptional regulation of TGF-beta1 target genes through SMAD cooperativity."xsd:string |
| http://purl.uniprot.org/citations/24613410 | http://purl.uniprot.org/core/volume | "26"xsd:string |
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