Differential RelA- and RelB-dependent gene transcription in LTβR-stimulated mouse embryonic fibroblasts

Background Lymphotoxin signaling via the lymphotoxin-β receptor (LTβR) has been implicated in biological processes ranging from development of secondary lymphoid organs, maintenance of spleen architecture, host defense against pathogens, autoimmunity, and lipid homeostasis. The major transcription f...

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Vydáno v:BMC genomics Ročník 9; číslo 1; s. 606
Hlavní autoři: Lovas, Agnes, Radke, Dörte, Albrecht, Daniela, Yilmaz, Z Buket, Möller, Ulrich, Habenicht, Andreas JR, Weih, Falk
Médium: Journal Article
Jazyk:angličtina
Vydáno: London BioMed Central 16.12.2008
BioMed Central Ltd
BMC
Témata:
Animal Genetics and Genomics
Biomedical and Life Sciences
Cellular signal transduction
DNA binding proteins
Fibroblasts
Genetic aspects
Health aspects
Life Sciences
Microarrays
Microbial Genetics and Genomics
Physiological aspects
Plant Genetics and Genomics
Proteomics
Research Article
Germany
Hepatic Lipase
Enrich Biological Process
Motif Ligand
Gene Ontology
Adipogenic Differentiation
ISSN:1471-2164, 1471-2164
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Shrnutí:Background Lymphotoxin signaling via the lymphotoxin-β receptor (LTβR) has been implicated in biological processes ranging from development of secondary lymphoid organs, maintenance of spleen architecture, host defense against pathogens, autoimmunity, and lipid homeostasis. The major transcription factor that is activated by LTβR crosslinking is NF-κB. Two signaling pathways have been described, the classical inhibitor of NF-κB α (IκBα)-regulated and the alternative p100-regulated pathway that result in the activation of p50-RelA and p52-RelB NF-κB heterodimers, respectively. Results Using microarray analysis, we investigated the transcriptional response downstream of the LTβR in mouse embryonic fibroblasts (MEFs) and its regulation by the RelA and RelB subunits of NF-κB. We describe novel LTβR-responsive genes that were regulated by RelA and/or RelB. The majority of LTβR-regulated genes required the presence of both RelA and RelB, revealing significant crosstalk between the two NF-κB activation pathways. Gene Ontology (GO) analysis confirmed that LTβR-NF-κB target genes are predominantly involved in the regulation of immune responses. However, other biological processes, such as apoptosis/cell death, cell cycle, angiogenesis, and taxis were also regulated by LTβR signaling. Moreover, LTβR activation inhibited expression of a key adipogenic transcription factor, peroxisome proliferator activated receptor-γ ( pparg ), suggesting that LTβR signaling may interfere with adipogenic differentiation. Conclusion Microarray analysis of LTβR-stimulated fibroblasts provided comprehensive insight into the transcriptional response of LTβR signaling and its regulation by the NF-κB family members RelA and RelB.
ISSN:1471-2164
1471-2164
DOI:10.1186/1471-2164-9-606