Smad7 dependent expression signature highlights BMP2 and HK2 signaling in HSC transdifferentiation.
OBJECTIVE
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.


CONCLUSIONS
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.
Interdisciplinary Centre for Clinical Research (IZKF) Aachen, RWTH Aachen University, 52074 Aachen, Germany.
Bernd
B
Denecke
Lucia
L
Wickert
Yan
Y
Liu
Loredana
L
Ciuclan
Steven
S
Dooley
Nadja M
NM
Meindl-Beinker
D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000235:genetics / Q000378:metabolism*; D054338:Cell Transdifferentiation / Q000502:physiology*; D002478:Cells, Cultured; D005260:Female; D005786:Gene Expression Regulation; D055166:Hepatic Stellate Cells / Q000502:physiology*; D008297:Male; D046228:Microarray Analysis; D008969:Molecular Sequence Data; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D015398:Signal Transduction / Q000502:physiology*; D051906:Smad7 Protein / Q000235:genetics / Q000378:metabolism*; D020840:Tissue Kallikreins / Q000235:genetics / Q000378:metabolism*
D055396:Bone Morphogenetic Protein 2; D051906:Smad7 Protein; D020840:Tissue Kallikreins