Systematic name M2444
Brief description Genes down-regulated in MEF cells (embryonic fibroblast) upon stimulation with TGFB1 [GeneID=7040] for 1 h.
Full description or abstract 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.
Collection C2: curated gene sets
      CGP: chemical and genetic perturbations
Source publication Pubmed 19752192   Authors: Plasari G,Calabrese A,Dusserre Y,Gronostajski RM,McNair A,Michalik L,Mermod N
Exact source Table 3S: 1h TGFB1 treated vs untreated: Fold change < 0
Related gene sets (show 9 additional gene sets from the source publication)
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Organism Mus musculus
Contributed by Arthur Liberzon (Broad Institute)
Source platform Mouse430_2
Dataset references (show 1 datasets)
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Compendia expression profiles Human tissue compendium (Novartis)
NCI-60 cell lines (National Cancer Institute)
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Version history 3.1: First introduced

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