Differential RelA- and RelB-dependent gene transcription in LTβR-stimulated mouse embryonic fibroblasts
<p>Abstract</p> <p>Background</p> <p>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, autoim...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2008-12-01
|
| Series: | BMC Genomics |
| Online Access: | http://www.biomedcentral.com/1471-2164/9/606 |
| _version_ | 1828475025234067456 |
|---|---|
| author | Yilmaz Z Buket Albrecht Daniela Radke Dörte Lovas Agnes Möller Ulrich Habenicht Andreas JR Weih Falk |
| author_facet | Yilmaz Z Buket Albrecht Daniela Radke Dörte Lovas Agnes Möller Ulrich Habenicht Andreas JR Weih Falk |
| author_sort | Yilmaz Z Buket |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>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.</p> <p>Results</p> <p>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 (<it>pparg</it>), suggesting that LTβR signaling may interfere with adipogenic differentiation.</p> <p>Conclusion</p> <p>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.</p> |
| first_indexed | 2024-12-11T06:06:56Z |
| format | Article |
| id | doaj.art-7d4447a4f9ef4068b77b9586a9425a1c |
| institution | Directory Open Access Journal |
| issn | 1471-2164 |
| language | English |
| last_indexed | 2024-12-11T06:06:56Z |
| publishDate | 2008-12-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Genomics |
| spelling | doaj.art-7d4447a4f9ef4068b77b9586a9425a1c2022-12-22T01:18:15ZengBMCBMC Genomics1471-21642008-12-019160610.1186/1471-2164-9-606Differential RelA- and RelB-dependent gene transcription in LTβR-stimulated mouse embryonic fibroblastsYilmaz Z BuketAlbrecht DanielaRadke DörteLovas AgnesMöller UlrichHabenicht Andreas JRWeih Falk<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Results</p> <p>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 (<it>pparg</it>), suggesting that LTβR signaling may interfere with adipogenic differentiation.</p> <p>Conclusion</p> <p>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.</p>http://www.biomedcentral.com/1471-2164/9/606 |
| spellingShingle | Yilmaz Z Buket Albrecht Daniela Radke Dörte Lovas Agnes Möller Ulrich Habenicht Andreas JR Weih Falk Differential RelA- and RelB-dependent gene transcription in LTβR-stimulated mouse embryonic fibroblasts BMC Genomics |
| title | Differential RelA- and RelB-dependent gene transcription in LTβR-stimulated mouse embryonic fibroblasts |
| title_full | Differential RelA- and RelB-dependent gene transcription in LTβR-stimulated mouse embryonic fibroblasts |
| title_fullStr | Differential RelA- and RelB-dependent gene transcription in LTβR-stimulated mouse embryonic fibroblasts |
| title_full_unstemmed | Differential RelA- and RelB-dependent gene transcription in LTβR-stimulated mouse embryonic fibroblasts |
| title_short | Differential RelA- and RelB-dependent gene transcription in LTβR-stimulated mouse embryonic fibroblasts |
| title_sort | differential rela and relb dependent gene transcription in ltβr stimulated mouse embryonic fibroblasts |
| url | http://www.biomedcentral.com/1471-2164/9/606 |
| work_keys_str_mv | AT yilmazzbuket differentialrelaandrelbdependentgenetranscriptioninltbrstimulatedmouseembryonicfibroblasts AT albrechtdaniela differentialrelaandrelbdependentgenetranscriptioninltbrstimulatedmouseembryonicfibroblasts AT radkedorte differentialrelaandrelbdependentgenetranscriptioninltbrstimulatedmouseembryonicfibroblasts AT lovasagnes differentialrelaandrelbdependentgenetranscriptioninltbrstimulatedmouseembryonicfibroblasts AT mollerulrich differentialrelaandrelbdependentgenetranscriptioninltbrstimulatedmouseembryonicfibroblasts AT habenichtandreasjr differentialrelaandrelbdependentgenetranscriptioninltbrstimulatedmouseembryonicfibroblasts AT weihfalk differentialrelaandrelbdependentgenetranscriptioninltbrstimulatedmouseembryonicfibroblasts |