STANDARD_NAME PLASARI_TGFB1_SIGNALING_VIA_NFIC_10HR_DN SYSTEMATIC_NAME M2455 COLLECTION C2:CGP MSIGDB_URL https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/PLASARI_TGFB1_SIGNALING_VIA_NFIC_10HR_DN NAMESPACE AFFY_Mouse430 DESCRIPTION_BRIEF Genes down-regulated after 10 h of TGFB1 [GeneID=7040] stimulation in MEF cells (embryonic fibroblast) with NFIC [GeneID=4782] knockout vs wild type MEFs. DESCRIPTION_FULL Transforming growth factor beta (TGF-beta) and platelet-derived growth factor A (PDGFAlpha) play a central role in tissue morphogenesis and repair, but their interplay remain poorly understood. The nuclear factor I C (NFI-C) transcription factor has been implicated in TGF-beta signaling, extracellular matrix deposition, and skin appendage pathologies, but a potential role in skin morphogenesis or healing had not been assessed. To evaluate this possibility, we performed a global gene expression analysis in NFI-C(-/-) and wild-type embryonic primary murine fibroblasts. This indicated that NFI-C acts mostly to repress gene expression in response to TGF-beta1. Misregulated genes were prominently overrepresented by regulators of connective tissue inflammation and repair. In vivo skin healing revealed a faster inflammatory stage and wound closure in NFI-C(-/-) mice. Expression of PDGFA and PDGF-receptor alpha were increased in wounds of NFI-C(-/-) mice, explaining the early recruitment of macrophages and fibroblasts. Differentiation of fibroblasts to contractile myofibroblasts was also elevated, providing a rationale for faster wound closure. Taken together with the role of TGF-beta in myofibroblast differentiation, our results imply a central role of NFI-C in the interplay of the two signaling pathways and in regulation of the progression of tissue regeneration. PMID 19752192 GEOID GSE15871 AUTHORS Plasari G,Calabrese A,Dusserre Y,Gronostajski RM,McNair A,Michalik L,Mermod N CONTRIBUTOR Arthur Liberzon CONTRIBUTOR_ORG MSigDB Team EXACT_SOURCE Table 4S: KO vs WT after 10h of TGFB1 treatment: Fold Change < 0 FILTERED_BY_SIMILARITY EXTERNAL_NAMES_FOR_SIMILAR_TERMS EXTERNAL_DETAILS_URL SOURCE_MEMBERS 1415965_at,1415999_at,1418357_at,1419015_at,1419120_at,1419125_at,1421001_a_at,1421917_at,1422024_at,1422628_at,1422631_at,1422808_s_at,1423327_at,1423895_a_at,1424010_at,1425133_s_at,1426913_at,1427395_a_at,1428391_at,1429259_a_at,1432517_a_at,1433434_at,1433465_a_at,1434140_at,1435375_at,1445274_at,1448754_at,1449484_at,1449827_at,1451716_at,1451805_at,1452492_a_at,1454671_at,1455034_at,1458683_at GENE_SYMBOLS SCD,HEY1,FOXG1,CCN5,LYL1,PTPN18,CA6,PDGFRA,FLI1,FAM111A,AHR,DOCK2,RPL39L,CELF2,MFAP4,RAB3IL1,LSS,ALDH1A3,RAB3IL1,UQCC6,NNMT,VWA5A,C16orf54,MCF2L,OTULINL,ZNF624,RBP1,STC2,ACAN,MAFB,PHIP,SLC37A2,INSIG1,NR4A2, FOUNDER_NAMES