STANDARD_NAME	VERRECCHIA_RESPONSE_TO_TGFB1_C3
SYSTEMATIC_NAME	M5321
COLLECTION	C2:CGP
MSIGDB_URL	https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/VERRECCHIA_RESPONSE_TO_TGFB1_C3
NAMESPACE	HUMAN_SEQ_ACCESSION
DESCRIPTION_BRIEF	Cluster 3: ECM related genes up-regulated in dermal fibroblasts within 30 min after TGFB1 [GeneID=7040] addition; returned rapidly to basal level after that.
DESCRIPTION_FULL	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.
PMID	11279127
GEOID	
AUTHORS	Verrecchia F,Chu ML,Mauviel A
CONTRIBUTOR	John Newman
CONTRIBUTOR_ORG	University of Washington
EXACT_SOURCE	Table 1: Cluster 3
FILTERED_BY_SIMILARITY	
EXTERNAL_NAMES_FOR_SIMILAR_TERMS	
EXTERNAL_DETAILS_URL	
SOURCE_MEMBERS	J05633,L16785,L25080,M31470,M34671,M35410,M65062,M74088,U14588,X70904,X92521,X94991,X95282,Y00285
GENE_SYMBOLS	ITGB5,NME2,RHOA,RHOQ,CD59,IGFBP2,IGFBP5,APC,PXN,LAMA4,MMP19,ZYX,RND3,IGF2R
FOUNDER_NAMES