| http://purl.uniprot.org/citations/18772333 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/18772333 | http://www.w3.org/2000/01/rdf-schema#comment | "Transforming growth factor-beta (TGF-beta) plays a key role in scleroderma pathogenesis. The transcription factor early growth response-1 (Egr-1) mediates the stimulation of collagen transcription elicited by TGF-beta and is necessary for the development of pulmonary fibrosis in mice. Here, we report that TGF-beta causes a time- and dose-dependent increase in Egr-1 protein and mRNA levels and enhanced transcription of the Egr-1 gene via serum response elements in normal fibroblasts. The ability of TGF-beta to stimulate Egr-1 was preserved in Smad3-null mice and in explanted Smad3-null fibroblasts. The response was blocked by a specific mitogen-activated protein kinase kinase 1 (MEK1) inhibitor but not by an ALK5 kinase inhibitor. Furthermore, MEK1 was phosphorylated by TGF-beta, which was sufficient to drive Egr-1 transactivation. Stimulation by TGF-beta enhanced the transcriptional activity of Elk-1 via the MEK-extracellular signal-regulated kinase 1/2 pathway. Bleomycin-induced scleroderma in the mouse was accompanied by increased Egr-1 accumulation in lesional fibroblasts. Furthermore, biopsies of lesional skin and lung from patients with scleroderma showed increased Egr-1 levels, which were highest in early diffuse disease. Moreover, both Egr-1 mRNA and protein were elevated in explanted scleroderma skin fibroblasts in vitro. Together, these findings define a Smad-independent TGF-beta signal transduction mechanism that underlies the stimulation of Egr-1, demonstrate for the first time sustained Egr-1 up-regulation in fibrotic lesions and suggests that Egr-1 has a role in the induction and progression of fibrosis."xsd:string |
| http://purl.uniprot.org/citations/18772333 | http://purl.org/dc/terms/identifier | "doi:10.2353/ajpath.2008.080382"xsd:string |
| http://purl.uniprot.org/citations/18772333 | http://purl.uniprot.org/core/author | "Mori Y."xsd:string |
| http://purl.uniprot.org/citations/18772333 | http://purl.uniprot.org/core/author | "Wu M."xsd:string |
| http://purl.uniprot.org/citations/18772333 | http://purl.uniprot.org/core/author | "Varga J."xsd:string |
| http://purl.uniprot.org/citations/18772333 | http://purl.uniprot.org/core/author | "Bhattacharyya S."xsd:string |
| http://purl.uniprot.org/citations/18772333 | http://purl.uniprot.org/core/author | "Chang E."xsd:string |
| http://purl.uniprot.org/citations/18772333 | http://purl.uniprot.org/core/author | "Takehara K."xsd:string |
| http://purl.uniprot.org/citations/18772333 | http://purl.uniprot.org/core/author | "Chen S.J."xsd:string |
| http://purl.uniprot.org/citations/18772333 | http://purl.uniprot.org/core/author | "Ning H."xsd:string |
| http://purl.uniprot.org/citations/18772333 | http://purl.uniprot.org/core/author | "Lakos G."xsd:string |
| http://purl.uniprot.org/citations/18772333 | http://purl.uniprot.org/core/author | "Warner-Blankenship M."xsd:string |
| http://purl.uniprot.org/citations/18772333 | http://purl.uniprot.org/core/author | "Feghali-Bostwick C."xsd:string |
| http://purl.uniprot.org/citations/18772333 | http://purl.uniprot.org/core/author | "Nihijima C."xsd:string |
| http://purl.uniprot.org/citations/18772333 | http://purl.uniprot.org/core/date | "2008"xsd:gYear |
| http://purl.uniprot.org/citations/18772333 | http://purl.uniprot.org/core/name | "Am J Pathol"xsd:string |
| http://purl.uniprot.org/citations/18772333 | http://purl.uniprot.org/core/pages | "1085-1099"xsd:string |
| http://purl.uniprot.org/citations/18772333 | http://purl.uniprot.org/core/title | "Smad-independent transforming growth factor-beta regulation of early growth response-1 and sustained expression in fibrosis: implications for scleroderma."xsd:string |
| http://purl.uniprot.org/citations/18772333 | http://purl.uniprot.org/core/volume | "173"xsd:string |
| http://purl.uniprot.org/citations/18772333 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/18772333 |
| http://purl.uniprot.org/citations/18772333 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/18772333 |
| http://purl.uniprot.org/uniprot/#_A0A089VKS7-mappedCitation-18772333 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/18772333 |
| http://purl.uniprot.org/uniprot/#_A2CG44-mappedCitation-18772333 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/18772333 |
| http://purl.uniprot.org/uniprot/#_A2CG45-mappedCitation-18772333 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/18772333 |