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...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Hauptverfasser: Denecke, Bernd (VerfasserIn) , Wickert, Lucia (VerfasserIn) , Liu, Yan (VerfasserIn) , Ciuclan, Loredana (VerfasserIn) , Dooley, Steven (VerfasserIn) , Meindl-Beinker, Nadja M. (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 7 November 2010
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
Volltext
Verfasserangaben:Bernd Denecke, Lucia Wickert, Yan Liu, Loredana Ciuclan, Steven Dooley, Nadja M. Meindl-Beinker
Beschreibung
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.
Beschreibung:Gesehen am 25.01.2024
Beschreibung:Online Resource
ISSN:2219-2840
DOI:10.3748/wjg.v16.i41.5211