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)-ß canonical signaling pathways on hepatic stellate cell (HSC) transdifferentiation in detail. METHODS: We systematically analysed genes regulated by TGF-ß/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-ß and BMP2 pathways in HSCs and (2) a Smad7 dependently decreased sugar metabolism ameliorates HSC activation probably by energy withdrawal.