Human Gene Set: VERRECCHIA_RESPONSE_TO_TGFB1_C5


Standard name VERRECCHIA_RESPONSE_TO_TGFB1_C5
Systematic name M6470
Brief description Cluster 5: ECM related genes up-regulated in dermal fibroblasts later than 30 min after TGFB1 [GeneID=7040] addition; decreased slowly after the peak at 120 min time point.
Full description or abstract Despite major advances in the understanding of the intimate mechanisms of transforming growth factor-beta (TGF-beta) signaling through the Smad pathway, little progress has been made in the identification of direct target genes. In this report, using cDNA microarrays, we have focussed our attention on the characterization of extracellular matrix-related genes rapidly induced by TGF-beta in human dermal fibroblasts and attempted to identify the ones whose up-regulation by TGF-beta is Smad-mediated. For a gene to qualify as a direct Smad target, we postulated that it had to meet the following criteria: (1) rapid (30 min) and significant (at least 2-fold) elevation of steady-state mRNA levels upon TGF-beta stimulation, (2) activation of the promoter by both exogenous TGF-beta and co-transfected Smad3 expression vector, (3) up-regulation of promoter activity by TGF-beta blocked by both dominant-negative Smad3 and inhibitory Smad7 expression vectors, and (4) promoter transactivation by TGF-beta not possible in Smad3(-/-) mouse embryo fibroblasts. Using this stringent approach, we have identified COL1A2, COL3A1, COL6A1, COL6A3, and tissue inhibitor of metalloproteases-1 as definite TGF-beta/Smad3 targets. Extrapolation of this approach to other extracellular matrix-related gene promoters also identified COL1A1 and COL5A2, but not COL6A2, as novel Smad targets. Together, these results represent a significant step toward the identification of novel, early-induced Smad-dependent TGF-beta target genes in fibroblasts.
Collection C2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 11279127   Authors: Verrecchia F,Chu ML,Mauviel A
Exact source Table 1: Cluster 5
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Source species Homo sapiens
Contributed by John Newman (University of Washington)
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identifier namespace		 HUMAN_SEQ_ACCESSION
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Version history 3.0: Renamed from TGFBETA_C5_UP

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