{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,15]],"date-time":"2026-08-15T00:11:36Z","timestamp":1786752696369,"version":"build-2736575974"},"reference-count":58,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2013,1,31]],"date-time":"2013-01-31T00:00:00Z","timestamp":1359590400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0055786","type":"journal-article","created":{"date-parts":[[2013,1,31]],"date-time":"2013-01-31T22:00:07Z","timestamp":1359669607000},"page":"e55786","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":65,"title":["Class II HDAC Inhibition Hampers Hepatic Stellate Cell Activation by Induction of MicroRNA-29"],"prefix":"10.1371","volume":"8","author":[{"given":"Inge","family":"Mannaerts","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Eysackers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oscar O.","family":"Onyema","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katrien","family":"Van Beneden","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio","family":"Valente","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonello","family":"Mai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margarete","family":"Odenthal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leo A.","family":"van Grunsven","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2013,1,31]]},"reference":[{"issue":"Suppl 2","key":"ref1","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1111\/j.1440-1746.2011.07002.x","article-title":"What's new in liver fibrosis? The origin of myofibroblasts in liver fibrosis","volume":"27","author":"K Iwaisako","year":"2012","journal-title":"J Gastroenterol Hepatol"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1152\/physrev.00013.2007","article-title":"Hepatic Stellate Cells: Protean, Multifunctional, and Enigmatic Cells of the Liver","volume":"88","author":"SL Friedman","year":"2008","journal-title":"Physiol Rev"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1055\/s-2001-17550","article-title":"History, heterogeneity, developmental biology, and functions of quiescent hepatic stellate cells","volume":"21","author":"A Geerts","year":"2001","journal-title":"Semin Liver Dis"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1016\/j.bbalip.2008.11.001","article-title":"Hepatic stellate cell lipid droplets: a specialized lipid droplet for retinoid storage","volume":"1791","author":"WS Blaner","year":"2009","journal-title":"Biochim Biophys Acta"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"1937","DOI":"10.1053\/j.gastro.2007.02.033","article-title":"Gene expression profiles during hepatic stellate cell activation in culture and in vivo","volume":"132","author":"S De Minicis","year":"2007","journal-title":"Gastroenterology"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"G709","DOI":"10.1152\/ajpgi.00451.2010","article-title":"Therapeutic targets in liver fibrosis","volume":"300","author":"JA Fallowfield","year":"2011","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1016\/j.jhep.2011.04.008","article-title":"Targeted therapy of liver fibrosis\/cirrhosis and its complications","volume":"55","author":"K Poelstra","year":"2011","journal-title":"J Hepatol"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"5163","DOI":"10.1111\/j.1742-4658.2009.07213.x","article-title":"Changes in microRNAs associated with hepatic stellate cell activation status identify signaling pathways","volume":"276","author":"CJ Guo","year":"2009","journal-title":"FEBS J"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1016\/j.febslet.2009.01.034","article-title":"Over-expressed microRNA-27a and 27b influence fat accumulation and cell proliferation during rat hepatic stellate cell activation","volume":"583","author":"J Ji","year":"2009","journal-title":"FEBS Lett"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/j.cell.2009.01.002","article-title":"MicroRNAs: target recognition and regulatory functions","volume":"136","author":"DP Bartel","year":"2009","journal-title":"Cell"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1002\/hep.23922","article-title":"Micro-RNA profiling reveals a role for miR-29 in human and murine liver fibrosis","volume":"53","author":"C Roderburg","year":"2011","journal-title":"Hepatology"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"e24568","DOI":"10.1371\/journal.pone.0024568","article-title":"Hepatocyte growth factor (HGF) inhibits collagen I and IV synthesis in hepatic stellate cells by miRNA-29 induction","volume":"6","author":"M Kwiecinski","year":"2011","journal-title":"PLoS ONE"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"49","DOI":"10.3389\/fphys.2012.00049","article-title":"microRNA are Central Players in Anti- and Profibrotic Gene Regulation during Liver Fibrosis","volume":"3","author":"A Noetel","year":"2012","journal-title":"Front Physiol"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1038\/sj.cdd.4401979","article-title":"Regulation of myofibroblast transdifferentiation by DNA methylation and MeCP2: implications for wound healing and fibrogenesis","volume":"14","author":"J Mann","year":"2007","journal-title":"Cell Death Differ"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"858","DOI":"10.1002\/hep.510290328","article-title":"A histone deacetylase inhibitor, trichostatin A, suppresses myofibroblastic differentiation of rat hepatic stellate cells in primary culture","volume":"29","author":"T Niki","year":"1999","journal-title":"Hepatology"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"788","DOI":"10.1016\/S0168-8278(02)00275-1","article-title":"Actin filament formation, reorganization and migration are impaired in hepatic stellate cells under influence of trichostatin A, a histone deacetylase inhibitor","volume":"37","author":"K Rombouts","year":"2002","journal-title":"Journal of Hepatology"},{"key":"ref17","first-page":"239","article-title":"Trichostatin A, lead compound for development of antifibrogenic drugs","volume":"64","author":"K Rombouts","year":"2001","journal-title":"Acta Gastroenterol Belg"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1002\/hep.23334","article-title":"Chronic administration of valproic acid inhibits activation of mouse hepatic stellate cells in vitro and in vivo","volume":"51","author":"I Mannaerts","year":"2010","journal-title":"Hepatology"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1042\/bj20021321","article-title":"Histone deacetylases (HDACs): characterization of the classical HDAC family","volume":"370","author":"AJ de Ruijter","year":"2003","journal-title":"Biochem J"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"8637","DOI":"10.1128\/MCB.00393-07","article-title":"Histone deacetylase 6 regulates growth factor-induced actin remodeling and endocytosis","volume":"27","author":"YS Gao","year":"2007","journal-title":"Mol Cell Biol"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1038\/417455a","article-title":"HDAC6 is a microtubule-associated deacetylase","volume":"417","author":"C Hubbert","year":"2002","journal-title":"Nature"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"1168","DOI":"10.1093\/emboj\/cdg115","article-title":"HDAC-6 interacts with and deacetylates tubulin and microtubules in vivo","volume":"22","author":"Y Zhang","year":"2003","journal-title":"Embo J"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"3344","DOI":"10.1021\/jm049002a","article-title":"Class II (IIa)-selective histone deacetylase inhibitors. 1. Synthesis and biological evaluation of novel (aryloxopropenyl)pyrrolyl hydroxyamides","volume":"48","author":"A Mai","year":"2005","journal-title":"J Med Chem"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1038\/embor.2009.88","article-title":"Selective class II HDAC inhibitors impair myogenesis by modulating the stability and activity of HDAC-MEF2 complexes","volume":"10","author":"A Nebbioso","year":"2009","journal-title":"EMBO Rep"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"2030","DOI":"10.1016\/j.bbamcr.2008.07.007","article-title":"HDAC-class II specific inhibition involves HDAC proteasome-dependent degradation mediated by RANBP2","volume":"1783","author":"A Scognamiglio","year":"2008","journal-title":"Biochimica et Biophysica Acta (BBA) - Molecular Cell Research"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1677\/JME-10-0043","article-title":"HDACs class II selective inhibition alters nuclear receptor dependent differentiation","volume":"45","author":"A Nebbioso","year":"2010","journal-title":"J Mol Endocrinol"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"5437","DOI":"10.1002\/pmic.200800866","article-title":"Histone post-translational modifications by HPLC-ESI-MS after HT29 cell treatment with histone deacetylase inhibitors","volume":"9","author":"M Naldi","year":"2009","journal-title":"PROTEOMICS"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1038\/onc.2009.306","article-title":"Histone deacetylase inhibitors induce thyroid cancer-specific apoptosis through proteasome-dependent inhibition of TRAIL degradation","volume":"29","author":"E Borbone","year":"2010","journal-title":"Oncogene"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1016\/j.jhep.2009.12.007","article-title":"Advanced glycation end products induce production of reactive oxygen species via the activation of NADPH oxidase in murine hepatic stellate cells","volume":"52","author":"EL Guimaraes","year":"2010","journal-title":"J Hepatol"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"5245","DOI":"10.1158\/0008-5472.CAN-04-0496","article-title":"Normalization of real-time quantitative reverse transcription-PCR data: a model-based variance estimation approach to identify genes suited for normalization, applied to bladder and colon cancer data sets","volume":"64","author":"CL Andersen","year":"2004","journal-title":"Cancer Res"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1023\/B:BILE.0000019559.84305.47","article-title":"Determination of stable housekeeping genes, differentially regulated target genes and sample integrity: BestKeeper\u2013Excel-based tool using pair-wise correlations","volume":"26","author":"MW Pfaffl","year":"2004","journal-title":"Biotechnol Lett"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"2795","DOI":"10.1073\/pnas.1013124108","article-title":"N\u03b5-lysine acetylation determines dissociation from GAP junctions and lateralization of connexin 43 in normal and dystrophic heart","volume":"108","author":"C Colussi","year":"2011","journal-title":"Proceedings of the National Academy of Sciences"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"2861","DOI":"10.2337\/db11-0440","article-title":"Specific control of pancreatic endocrine beta- and delta-cell mass by class IIa histone deacetylases HDAC4, HDAC5, and HDAC9","volume":"60","author":"O Lenoir","year":"2011","journal-title":"Diabetes"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"1747","DOI":"10.1016\/j.bcp.2007.08.023","article-title":"Antifibrogenic effects of histone deacetylase inhibitors on pancreatic stellate cells","volume":"74","author":"R Bulow","year":"2007","journal-title":"Biochem Pharmacol"},{"key":"ref35","first-page":"928326","article-title":"Roles and targets of class I and IIa histone deacetylases in cardiac hypertrophy","volume":"2011","author":"HJ Kee","year":"2011","journal-title":"J Biomed Biotechnol"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1124\/jpet.110.168385","article-title":"Histone Deacetylase: A Potential Therapeutic Target for Fibrotic Disorders","volume":"335","author":"M Pang","year":"2010","journal-title":"Journal of Pharmacology and Experimental Therapeutics"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"1863","DOI":"10.1681\/ASN.2010111196","article-title":"Valproic acid attenuates proteinuria and kidney injury","volume":"22","author":"K Van Beneden","year":"2011","journal-title":"J Am Soc Nephrol"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1016\/j.bbrc.2009.11.056","article-title":"Suppression of type I collagen production by microRNA-29b in cultured human stellate cells","volume":"391","author":"T Ogawa","year":"2009","journal-title":"Biochemical and Biophysical Research Communications"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1161\/CIRCRESAHA.109.209338","article-title":"Protein Acetylation in the Cardiorenal Axis: The Promise of Histone Deacetylase Inhibitors","volume":"106","author":"EW Bush","year":"2009","journal-title":"Circ Res"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"10014","DOI":"10.1073\/pnas.180316197","article-title":"Histone deacetylase inhibitor selectively induces p21WAF1 expression and gene-associated histone acetylation","volume":"97","author":"VM Richon","year":"2000","journal-title":"Proceedings of the National Academy of Sciences"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1002\/ajh.1174","article-title":"Histone deacetylase inhibitors increase p21WAF1 and induce apoptosis of human myeloma cell lines independent of decreased IL-6 receptor expression","volume":"68","author":"D Lavelle","year":"2001","journal-title":"American Journal of Hematology"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"G1147","DOI":"10.1152\/ajpgi.00032.2007","article-title":"Increased stiffness of the rat liver precedes matrix deposition: implications for fibrosis","volume":"293","author":"PC Georges","year":"2007","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"key":"ref43","article-title":"Hepatic Stellate Cells Require a Stiff Environment for Myofibroblastic Differentiation","author":"AL Olsen","year":"2011","journal-title":"American Journal of Physiology - Gastrointestinal and Liver Physiology"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"1572","DOI":"10.1016\/j.bbamcr.2007.05.016","article-title":"Histone deacetylase 4 is required for TGFbeta1-induced myofibroblastic differentiation","volume":"1773","author":"W Glenisson","year":"2007","journal-title":"Biochim Biophys Acta"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"L864","DOI":"10.1152\/ajplung.00128.2009","article-title":"Abrogation of TGF-beta1-induced fibroblast-myofibroblast differentiation by histone deacetylase inhibition","volume":"297","author":"W Guo","year":"2009","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"1915","DOI":"10.2353\/ajpath.2010.100011","article-title":"Epigenetic Repression of Matrix Metalloproteinases in Myofibroblastic Hepatic Stellate Cells through Histone Deacetylases 4. Implication in Tissue Fibrosis","volume":"177","author":"L Qin","year":"2010","journal-title":"Am J Pathol"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1182\/blood-2011-12-394494","article-title":"Cocktail of eternity: HDAC meets miR","volume":"119","author":"CM Wendtner","year":"2012","journal-title":"Blood"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"1162","DOI":"10.1182\/blood-2011-05-351510","article-title":"Histone deacetylases mediate the silencing of miR-15a, miR-16, and miR-29b in chronic lymphocytic leukemia","volume":"119","author":"D Sampath","year":"2012","journal-title":"Blood"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1124\/jpet.107.122481","article-title":"Cyclic Arg-Gly-Asp peptide-labeled liposomes for targeting drug therapy of hepatic fibrosis in rats","volume":"322","author":"SL Du","year":"2007","journal-title":"J Pharmacol Exp Ther"},{"key":"ref50","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/j.jconrel.2011.12.023","article-title":"Effects of interferon-gamma liposomes targeted to platelet-derived growth factor receptor-beta on hepatic fibrosis in rats","volume":"159","author":"F Li","year":"2012","journal-title":"J Control Release"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1053\/j.gastro.2006.04.012","article-title":"Pregnane X receptor activators inhibit human hepatic stellate cell transdifferentiation in vitro","volume":"131","author":"EL Haughton","year":"2006","journal-title":"Gastroenterology"},{"key":"ref52","first-page":"937","article-title":"Inhibitory effects of antisense oligonucleotides on the expression of procollagen type III gene in mouse hepatic stellate cells transformed by simian virus 40doi:10.1046\/j.1440-1827.2000.01146.x","volume":"50","author":"S Horie","year":"2000","journal-title":"Pathology International"},{"key":"ref53","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.bbrc.2007.12.085","article-title":"Canonical Wnt signaling maintains the quiescent stage of hepatic stellate cells","volume":"367","author":"C Kordes","year":"2008","journal-title":"Biochemical and Biophysical Research Communications"},{"key":"ref54","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1111\/j.1872-034X.2008.00485.x","article-title":"Resveratrol amplifies profibrogenic effects of free fatty acids on human hepatic stellate cells","volume":"396","author":"LP Bechmann","year":"2009","journal-title":"Hepatology Research"},{"key":"ref55","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1007\/s11095-005-9043-5","article-title":"Smad3 Specific Inhibitor, Naringenin, Decreases the Expression of Extracellular Matrix Induced by TGF-\u03b21 in Cultured Rat Hepatic Stellate Cells","volume":"23","author":"X Liu","year":"2006","journal-title":"Pharmaceutical Research"},{"key":"ref56","doi-asserted-by":"crossref","first-page":"15090","DOI":"10.1074\/jbc.M600030200","article-title":"Halofuginone induces matrix metalloproteinases in rat hepatic stellate cells via activation of p38 and NFkappaB","volume":"281","author":"Y Popov","year":"2006","journal-title":"J Biol Chem"},{"key":"ref57","doi-asserted-by":"crossref","first-page":"1587","DOI":"10.1016\/j.bbagen.2006.09.012","article-title":"Effects of rhDecorin on TGF-beta1 induced human hepatic stellate cells LX-2 activation","volume":"1760","author":"YF Shi","year":"2006","journal-title":"Biochim Biophys Acta"},{"key":"ref58","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1007\/s10620-009-0743-2","article-title":"The GABA(B) Receptor Inhibits Activation of Hepatic Stellate Cells","volume":"55","author":"F Xiao","year":"2009","journal-title":"Dig Dis Sci"}],"container-title":["PLoS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0055786","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2018,10,22]],"date-time":"2018-10-22T16:49:14Z","timestamp":1540226954000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0055786"}},"subtitle":[],"editor":[{"given":"Rajasingh","family":"Johnson","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2013,1,31]]},"references-count":58,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2013,1,31]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0055786","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,1,31]]}}}