Smad7 dependent expression signature highlights BMP2 and HK2 signaling in HSC transdifferentiation
AIM: To analyse the influence of Smad7, antagonist of transforming growth factor (TGF)-β canonical signaling pathways on hepatic stellate cell (HSC) transdifferentiation in detail. - METHODS: We systematically analysed genes regulated by TGF-β/Smad7 in activated HSCs by microarray analysis and valid...
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| Hauptverfasser: | , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
7 November 2010
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| In: |
World journal of gastroenterology
Year: 2010, Jahrgang: 16, Heft: 41, Pages: 5211-5224 |
| ISSN: | 2219-2840 |
| DOI: | 10.3748/wjg.v16.i41.5211 |
| Online-Zugang: | Verlag, kostenfrei, Volltext: https://doi.org/10.3748/wjg.v16.i41.5211 |
| Verfasserangaben: | Bernd Denecke, Lucia Wickert, Yan Liu, Loredana Ciuclan, Steven Dooley, Nadja M. Meindl-Beinker |
| Zusammenfassung: | AIM: To analyse the influence of Smad7, antagonist of transforming growth factor (TGF)-β canonical signaling pathways on hepatic stellate cell (HSC) transdifferentiation in detail. - METHODS: We systematically analysed genes regulated by TGF-β/Smad7 in activated HSCs by microarray analysis and validated the results using real time polymerase chain reaction and Western blotting analysis. - RESULTS: We identified 100 known and unknown targets underlying the regulation of Smad7 expression and delineated 8 gene ontology groups. Hk2, involved in glycolysis, was one of the most downregulated proteins, while BMP2, activator of the Smad1/5/8 pathway, was extremely upregulated by Smad7. However, BMP2 dependent Smad1 activation could be inhibited in vitro by Smad7 overexpression in HSCs. - CONCLUSION: We conclude (1) the existence of a tight crosstalk of TGF-β and BMP2 pathways in HSCs and (2) a Smad7 dependently decreased sugar metabolism ameliorates HSC activation probably by energy withdrawal. |
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| Beschreibung: | Gesehen am 25.01.2024 |
| Beschreibung: | Online Resource |
| ISSN: | 2219-2840 |
| DOI: | 10.3748/wjg.v16.i41.5211 |