Mouse Gene Set: SEKI_INFLAMMATORY_RESPONSE_LPS_DN

For the Human gene set with the same name, see SEKI_INFLAMMATORY_RESPONSE_LPS_DN

Standard name SEKI_INFLAMMATORY_RESPONSE_LPS_DN
Systematic name MM793
Brief description Genes down-regulated in hepatic stellar cells after stimulation with bacterial lipopolysacharide (LPS).
Full description or abstract Hepatic injury is associated with a defective intestinal barrier and increased hepatic exposure to bacterial products. Here we report that the intestinal bacterial microflora and a functional Toll-like receptor 4 (TLR4), but not TLR2, are required for hepatic fibrogenesis. Using Tlr4-chimeric mice and in vivo lipopolysaccharide (LPS) challenge, we demonstrate that quiescent hepatic stellate cells (HSCs), the main precursors for myofibroblasts in the liver, are the predominant target through which TLR4 ligands promote fibrogenesis. In quiescent HSCs, TLR4 activation not only upregulates chemokine secretion and induces chemotaxis of Kupffer cells, but also downregulates the transforming growth factor (TGF)-beta pseudoreceptor Bambi to sensitize HSCs to TGF-beta-induced signals and allow for unrestricted activation by Kupffer cells. LPS-induced Bambi downregulation and sensitization to TGF-beta is mediated by a MyD88-NF-kappaB-dependent pathway. Accordingly, Myd88-deficient mice have decreased hepatic fibrosis. Thus, modulation of TGF-beta signaling by a TLR4-MyD88-NF-kappaB axis provides a novel link between proinflammatory and profibrogenic signals.
Collection M2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 17952090   Authors: Seki E,De Minicis S,Osterreicher CH,Kluwe J,Osawa Y,Brenner DA,Schwabe RF
Exact source Table 1S: Fold change < 0.5
Related gene sets (show 1 additional gene sets from the source publication)
External links
Filtered by similarity ?
Source species Mus musculus
Contributed by Jessica Robertson (MSigDB Team)
Source platform or
identifier namespace		 AFFY_Mouse430
Dataset references  
Download gene set format: grp | gmt | xml | json | TSV metadata
Compute overlaps ? (show collections to investigate for overlap with this gene set)
Compendia expression profiles ? NG-CHM interactive heatmaps
(Please note that clustering takes a few seconds)
Mouse Transcriptomic BodyMap compendium

Legacy heatmaps (PNG)
Mouse Transcriptomic BodyMap compendium
Advanced query Further investigate these 23 genes
Show members (show 26 source identifiers mapped to 23 genes)
Version history 2022.1.Mm: First Introduced.


Creative Commons Attribution 4.0 International License (CC-BY-4.0)

The contents of this gene set are protected by copyright (c) 2004-2026 Broad Institute, Inc., Massachusetts Institute of Technology, and Regents of the University of California, subject to the terms and conditions of the Creative Commons Attribution 4.0 International License.

See the full MSigDB license terms here.