%0 Journal Article %A Feng, Teng %A Dzieran, Johanna %A Gu, Xing %A Marhenke, Silke %A Vogel, Arndt %A Machida, Keigo %A Weiss, Thomas S %A Ruemmele, Petra %A Kollmar, Otto %A Hoffmann, Patrick %A Grässer, Friedrich %A Allgayer, Heike %A Fabian, Jasmin %A Weng, Hong Lei %A Teufel, Andreas %A Maass, Thorsten %A Meyer, Christoph %A Lehmann, Ulrich %A Zhu, Cheng %A Mertens, Peter R %A Gao, Chun Fang %A Dooley, Steven %A Meindl-Beinker, Nadja M %T Smad7 regulates compensatory hepatocyte proliferation in damaged mouse liver and positively relates to better clinical outcome in human hepatocellular carcinoma. %J Clinical science %V 128 %N 11 %@ 1470-8736 %C London %I Portland %M DKFZ-2017-02532 %P 761 - 774 %D 2015 %X Transforming growth factor β (TGF-β) is cytostatic towards damage-induced compensatory hepatocyte proliferation. This function is frequently lost during hepatocarcinogenesis, thereby switching the TGF-β role from tumour suppressor to tumour promoter. In the present study, we investigate Smad7 overexpression as a pathophysiological mechanism for cytostatic TGF-β inhibition in liver damage and hepatocellular carcinoma (HCC). Transgenic hepatocyte-specific Smad7 overexpression in damaged liver of fumarylacetoacetate hydrolase (FAH)-deficient mice increased compensatory proliferation of hepatocytes. Similarly, modulation of Smad7 expression changed the sensitivity of Huh7, FLC-4, HLE and HLF HCC cell lines for cytostatic TGF-β effects. In our cohort of 140 HCC patients, Smad7 transcripts were elevated in 41.4 %K Smad7 Protein (NLM Chemicals) %K Transforming Growth Factor beta (NLM Chemicals) %K Y-Box-Binding Protein 1 (NLM Chemicals) %K YBX1 protein, human (NLM Chemicals) %F PUB:(DE-HGF)16 %9 Journal Article %$ pmid:25602745 %R 10.1042/CS20140606 %U https://inrepo02.dkfz.de/record/126504