{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T10:37:54Z","timestamp":1785407874770,"version":"3.56.0"},"reference-count":48,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2016,12,22]],"date-time":"2016-12-22T00:00:00Z","timestamp":1482364800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2016,12,22]],"date-time":"2016-12-22T00:00:00Z","timestamp":1482364800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Commun"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Hepatic stellate cell (HSC) activation on liver injury facilitates fibrosis. Hepatokines affecting HSCs are largely unknown. Here we show that hepcidin inhibits HSC activation and ameliorates liver fibrosis. We observe that hepcidin levels are inversely correlated with exacerbation of fibrosis in patients, and also confirm the relationship in animal models. Adenoviral delivery of hepcidin to mice attenuates liver fibrosis induced by CCl<jats:sub>4<\/jats:sub> treatment or bile duct ligation. In cell-based assays, either hepcidin from hepatocytes or exogenous hepcidin suppresses HSC activation by inhibiting TGF\u03b21-mediated Smad3 phosphorylation via Akt. In activated HSCs, ferroportin is upregulated, which can be prevented by hepcidin treatment. Similarly, ferroportin knockdown in HSCs prohibits TGF\u03b21-inducible Smad3 phosphorylation and increases Akt phosphorylation, whereas ferroportin over-expression has the opposite effect. HSC-specific ferroportin deletion also ameliorates liver fibrosis. In summary, hepcidin suppresses liver fibrosis by impeding TGF\u03b21-induced Smad3 phosphorylation in HSCs, which depends on Akt activated by a deficiency of ferroportin.<\/jats:p>","DOI":"10.1038\/ncomms13817","type":"journal-article","created":{"date-parts":[[2016,12,22]],"date-time":"2016-12-22T10:31:59Z","timestamp":1482402719000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":65,"title":["Hepcidin inhibits Smad3 phosphorylation in hepatic stellate cells by impeding ferroportin-mediated regulation of Akt"],"prefix":"10.1038","volume":"7","author":[{"given":"Chang Yeob","family":"Han","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5738-1105","authenticated-orcid":false,"given":"Ja Hyun","family":"Koo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sung Hoon","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Gardenghi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Rivella","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pavel","family":"Strnad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Se Jin","family":"Hwang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang Geon","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,12,22]]},"reference":[{"key":"BFncomms13817_CR1","doi-asserted-by":"publisher","first-page":"910","DOI":"10.1016\/j.jhep.2004.02.005","volume":"40","author":"A Mabuchi","year":"2004","unstructured":"Mabuchi, A. et al. Role of hepatic stellate cell\/hepatocyte interaction and activation of hepatic stellate cells in the early phase of liver regeneration in the rat. J. Hepatol. 40, 910\u2013916 (2004).","journal-title":"J. Hepatol."},{"key":"BFncomms13817_CR2","doi-asserted-by":"publisher","first-page":"1617","DOI":"10.1002\/hep.23184","volume":"50","author":"I Sawitza","year":"2009","unstructured":"Sawitza, I., Kordes, C., Reister, S. & Haussinger, D. The niche of stellate cells within rat liver. Hepatology 50, 1617\u20131624 (2009).","journal-title":"Hepatology"},{"key":"BFncomms13817_CR3","doi-asserted-by":"publisher","first-page":"2533","DOI":"10.1158\/0008-5472.CAN-11-3317","volume":"72","author":"C Coulouarn","year":"2012","unstructured":"Coulouarn, C. et al. Hepatocyte-stellate cell cross-talk in the liver engenders a permissive inflammatory microenvironment that drives progression in hepatocellular carcinoma. Cancer Res. 72, 2533\u20132542 (2012).","journal-title":"Cancer Res."},{"key":"BFncomms13817_CR4","doi-asserted-by":"publisher","first-page":"1319","DOI":"10.1053\/j.gastro.2012.07.115","volume":"143","author":"Y Chen","year":"2012","unstructured":"Chen, Y. et al. Hedgehog controls hepatic stellate cell fate by regulating metabolism. Gastroenterology 143, 1319\u20131329.e11 (2012).","journal-title":"Gastroenterology"},{"key":"BFncomms13817_CR5","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1146\/annurev-pathol-011110-130246","volume":"6","author":"V Hernandez-Gea","year":"2011","unstructured":"Hernandez-Gea, V. & Friedman, S. L. Pathogenesis of liver fibrosis. Annu. Rev. Pathol. 6, 425\u2013456 (2011).","journal-title":"Annu. Rev. Pathol."},{"key":"BFncomms13817_CR6","doi-asserted-by":"publisher","first-page":"2823","DOI":"10.1038\/ncomms3823","volume":"4","author":"I Mederacke","year":"2013","unstructured":"Mederacke, I. et al. Fate tracing reveals hepatic stellate cells as dominant contributors to liver fibrosis independent of its aetiology. Nat. Commun. 4, 2823 (2013).","journal-title":"Nat. Commun."},{"key":"BFncomms13817_CR7","doi-asserted-by":"publisher","first-page":"920","DOI":"10.1016\/j.jhep.2011.05.008","volume":"55","author":"P Dongiovanni","year":"2011","unstructured":"Dongiovanni, P., Fracanzani, A. L., Fargion, S. & Valenti, L. Iron in fatty liver and in the metabolic syndrome: a promising therapeutic target. J. Hepatol. 55, 920\u2013932 (2011).","journal-title":"J. Hepatol."},{"key":"BFncomms13817_CR8","doi-asserted-by":"publisher","first-page":"489","DOI":"10.1146\/annurev.pathol.4.110807.092205","volume":"4","author":"PL Lee","year":"2009","unstructured":"Lee, P. L. & Beutler, E. Regulation of hepcidin and iron-overload disease. Annu. Rev. Pathol. 4, 489\u2013515 (2009).","journal-title":"Annu. Rev. Pathol."},{"key":"BFncomms13817_CR9","doi-asserted-by":"publisher","first-page":"2090","DOI":"10.1126\/science.1104742","volume":"306","author":"E Nemeth","year":"2004","unstructured":"Nemeth, E. et al. Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization. Science 306, 2090\u20132093 (2004).","journal-title":"Science"},{"key":"BFncomms13817_CR10","doi-asserted-by":"publisher","first-page":"1509","DOI":"10.1182\/blood-2003-07-2378","volume":"103","author":"AS Zhang","year":"2004","unstructured":"Zhang, A. S., Xiong, S., Tsukamoto, H. & Enns, C. A. Localization of iron metabolism-related mRNAs in rat liver indicate that HFE is expressed predominantly in hepatocytes. Blood 103, 1509\u20131514 (2004).","journal-title":"Blood"},{"key":"BFncomms13817_CR11","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1172\/JCI24282","volume":"115","author":"R Bataller","year":"2005","unstructured":"Bataller, R. & Brenner, D. A. Liver fibrosis. J. Clin. Invest. 115, 209\u2013218 (2005).","journal-title":"J. Clin. Invest."},{"key":"BFncomms13817_CR12","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1007\/s00441-011-1246-y","volume":"347","author":"S Dooley","year":"2012","unstructured":"Dooley, S. & ten Dijke, P. TGF-beta in progression of liver disease. Cell Tissue Res. 347, 245\u2013256 (2012).","journal-title":"Cell Tissue Res."},{"key":"BFncomms13817_CR13","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1136\/gut.2004.042127","volume":"54","author":"L Xu","year":"2005","unstructured":"Xu, L. et al. Human hepatic stellate cell lines, LX-1 and LX-2: new tools for analysis of hepatic fibrosis. Gut. 54, 142\u2013151 (2005).","journal-title":"Gut."},{"key":"BFncomms13817_CR14","doi-asserted-by":"publisher","first-page":"1261","DOI":"10.1053\/j.gastro.2010.12.037","volume":"140","author":"C Brasse-Lagnel","year":"2011","unstructured":"Brasse-Lagnel, C. et al. Intestinal DMT1 cotransporter is down-regulated by hepcidin via proteasome internalization and degradation. Gastroenterology. 140, 1261\u20131271.e1 (2011).","journal-title":"Gastroenterology."},{"key":"BFncomms13817_CR15","doi-asserted-by":"publisher","first-page":"577","DOI":"10.1038\/nature02006","volume":"425","author":"R Derynck","year":"2003","unstructured":"Derynck, R. & Zhang, Y. E. Smad-dependent and Smad-independent pathways in TGF-beta family signalling. Nature 425, 577\u2013584 (2003).","journal-title":"Nature"},{"key":"BFncomms13817_CR16","doi-asserted-by":"publisher","first-page":"366","DOI":"10.1038\/ncb1117","volume":"6","author":"AR Conery","year":"2004","unstructured":"Conery, A. R. et al. Akt interacts directly with Smad3 to regulate the sensitivity to TGF-beta induced apoptosis. Nat. Cell Biol. 6, 366\u2013372 (2004).","journal-title":"Nat. Cell Biol."},{"key":"BFncomms13817_CR17","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1038\/sj.emboj.7600917","volume":"25","author":"K Song","year":"2006","unstructured":"Song, K., Wang, H., Krebs, T. L. & Danielpour, D. Novel roles of Akt and mTOR in suppressing TGF-beta\/ALK5-mediated Smad3 activation. EMBO J. 25, 58\u201369 (2006).","journal-title":"EMBO J."},{"key":"BFncomms13817_CR18","doi-asserted-by":"publisher","first-page":"350","DOI":"10.1042\/bst0320350","volume":"32","author":"ZZ Yang","year":"2004","unstructured":"Yang, Z. Z. et al. Physiological functions of protein kinase B\/Akt. Biochem. Soc. Trans. 32, 350\u2013354 (2004).","journal-title":"Biochem. Soc. Trans."},{"key":"BFncomms13817_CR19","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/j.bcmd.2012.03.002","volume":"49","author":"A Sukumaran","year":"2012","unstructured":"Sukumaran, A., Venkatraman, A. & Jacob, M. Inflammation-induced effects on iron-related proteins in splenic macrophages and the liver in mice. Blood Cells Mol. Dis. 49, 11\u201319 (2012).","journal-title":"Blood Cells Mol. Dis."},{"key":"BFncomms13817_CR20","doi-asserted-by":"publisher","first-page":"328","DOI":"10.1182\/blood-2005-05-2049","volume":"107","author":"E Nemeth","year":"2006","unstructured":"Nemeth, E. et al. The N-terminus of hepcidin is essential for its interaction with ferroportin: structure-function study. Blood 107, 328\u2013333 (2006).","journal-title":"Blood"},{"key":"BFncomms13817_CR21","doi-asserted-by":"publisher","first-page":"1801","DOI":"10.1002\/hep.26511","volume":"58","author":"G Xie","year":"2013","unstructured":"Xie, G. et al. Cross-talk between Notch and Hedgehog regulates hepatic stellate cell fate in mice. Hepatology 58, 1801\u20131813 (2013).","journal-title":"Hepatology"},{"key":"BFncomms13817_CR22","doi-asserted-by":"publisher","first-page":"633","DOI":"10.1016\/j.jhep.2014.04.034","volume":"61","author":"M Lunova","year":"2014","unstructured":"Lunova, M. et al. Hepcidin knockout mice fed with iron-rich diet develop chronic liver injury and liver fibrosis due to lysosomal iron overload. J. Hepatol. 61, 633\u2013641 (2014).","journal-title":"J. Hepatol."},{"key":"BFncomms13817_CR23","doi-asserted-by":"publisher","first-page":"4068","DOI":"10.1128\/MCB.00723-12","volume":"32","author":"ER Anderson","year":"2012","unstructured":"Anderson, E. R. et al. The hypoxia-inducible factor-C\/EBPalpha axis controls ethanol-mediated hepcidin repression. Mol. Cell Biol. 32, 4068\u20134077 (2012).","journal-title":"Mol. Cell Biol."},{"key":"BFncomms13817_CR24","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1002\/hep.25615","volume":"56","author":"JB Goodnough","year":"2012","unstructured":"Goodnough, J. B., Ramos, E., Nemeth, E. & Ganz, T. Inhibition of hepcidin transcription by growth factors. Hepatology 56, 291\u2013299 (2012).","journal-title":"Hepatology"},{"key":"BFncomms13817_CR25","doi-asserted-by":"publisher","first-page":"1052","DOI":"10.1016\/j.jhep.2012.06.015","volume":"57","author":"F D'Alessio","year":"2012","unstructured":"D'Alessio, F., Hentze, M. W. & Muckenthaler, M. U. The hemochromatosis proteins HFE, TfR2, and HJV form a membrane-associated protein complex for hepcidin regulation. J. Hepatol. 57, 1052\u20131060 (2012).","journal-title":"J. Hepatol."},{"key":"BFncomms13817_CR26","doi-asserted-by":"publisher","first-page":"11721","DOI":"10.1074\/jbc.M207728200","volume":"278","author":"C Liu","year":"2003","unstructured":"Liu, C. et al. Smads 2 and 3 are differentially activated by transforming growth factor-beta (TGF-beta ) in quiescent and activated hepatic stellate cells. Constitutive nuclear localization of Smads in activated cells is TGF-beta-independent. J. Biol. Chem. 278, 11721\u201311728 (2003).","journal-title":"J. Biol. Chem."},{"key":"BFncomms13817_CR27","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1053\/j.gastro.2015.09.039","volume":"150","author":"JH Koo","year":"2016","unstructured":"Koo, J. H., Lee, H. J., Kim, W. & Kim, S. G. Endoplasmic reticulum stress in hepatic stellate cells promotes liver fibrosis via PERK-mediated degradation of HNRNPA1 and up-regulation of SMAD2. Gastroenterology 150, 181\u2013193.e8 (2016).","journal-title":"Gastroenterology"},{"key":"BFncomms13817_CR28","doi-asserted-by":"publisher","first-page":"961","DOI":"10.1002\/hep.25746","volume":"56","author":"Z Zhang","year":"2012","unstructured":"Zhang, Z. et al. Ferroportin1 in hepatocytes and macrophages is required for the efficient mobilization of body iron stores in mice. Hepatology 56, 961\u2013971 (2012).","journal-title":"Hepatology"},{"key":"BFncomms13817_CR29","doi-asserted-by":"publisher","first-page":"640","DOI":"10.1016\/j.nutres.2009.09.007","volume":"29","author":"M Ndong","year":"2009","unstructured":"Ndong, M. et al. Iron deficiency down-regulates the Akt\/TSC1-TSC2\/mammalian target of rapamycin signaling pathway in rats and in COS-1 cells. Nutr, Res. 29, 640\u2013647 (2009).","journal-title":"Nutr, Res."},{"key":"BFncomms13817_CR30","doi-asserted-by":"publisher","first-page":"1139","DOI":"10.1016\/S0006-2952(02)01257-1","volume":"64","author":"C Gardi","year":"2002","unstructured":"Gardi, C., Arezzini, B., Fortino, V. & Comporti, M. Effect of free iron on collagen synthesis, cell proliferation and MMP-2 expression in rat hepatic stellate cells. Biochem. Pharmacol. 64, 1139\u20131145 (2002).","journal-title":"Biochem. Pharmacol."},{"key":"BFncomms13817_CR31","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1038\/nrm3330","volume":"13","author":"MS Song","year":"2012","unstructured":"Song, M. S., Salmena, L. & Pandolfi, P. P. The functions and regulation of the PTEN tumour suppressor. Nat. Rev. Mol. Cell Biol. 13, 283\u2013296 (2012).","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"BFncomms13817_CR32","doi-asserted-by":"publisher","first-page":"1512","DOI":"10.1002\/hep.23186","volume":"50","author":"G Son","year":"2009","unstructured":"Son, G., Hines, I. N., Lindquist, J., Schrum, L. W. & Rippe, R. A. Inhibition of phosphatidylinositol 3-kinase signaling in hepatic stellate cells blocks the progression of hepatic fibrosis. Hepatology 50, 1512\u20131523 (2009).","journal-title":"Hepatology"},{"key":"BFncomms13817_CR33","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1016\/j.biopha.2013.03.014","volume":"67","author":"J Wei","year":"2013","unstructured":"Wei, J., Feng, L., Li, Z., Xu, G. & Fan, X. MicroRNA-21 activates hepatic stellate cells via PTEN\/Akt signaling. Biomed. Pharmacother. 67, 387\u2013392 (2013).","journal-title":"Biomed. Pharmacother."},{"key":"BFncomms13817_CR34","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1172\/JCI200522675","volume":"115","author":"JS Duffield","year":"2005","unstructured":"Duffield, J. S. et al. Selective depletion of macrophages reveals distinct, opposing roles during liver injury and repair. J. Clin. Invest. 115, 56\u201365 (2005).","journal-title":"J. Clin. Invest."},{"key":"BFncomms13817_CR35","doi-asserted-by":"publisher","first-page":"2395","DOI":"10.1172\/JCI42011","volume":"120","author":"I De Domenico","year":"2010","unstructured":"De Domenico, I. et al. Hepcidin mediates transcriptional changes that modulate acute cytokine-induced inflammatory responses in mice. J. Clin. Invest. 120, 2395\u20132405 (2010).","journal-title":"J. Clin. Invest."},{"key":"BFncomms13817_CR36","doi-asserted-by":"publisher","first-page":"658","DOI":"10.1111\/j.1872-034X.2012.01111.x","volume":"43","author":"J Chang","year":"2013","unstructured":"Chang, J. et al. Activated hepatic stellate cells mediate the differentiation of macrophages. Hepatol. Res. 43, 658\u2013669 (2013).","journal-title":"Hepatol. Res."},{"key":"BFncomms13817_CR37","doi-asserted-by":"publisher","first-page":"3829","DOI":"10.1182\/blood-2012-07-440743","volume":"120","author":"E Ramos","year":"2012","unstructured":"Ramos, E. et al. Minihepcidins prevent iron overload in a hepcidin-deficient mouse model of severe hemochromatosis. Blood 120, 3829\u20133836 (2012).","journal-title":"Blood"},{"key":"BFncomms13817_CR38","doi-asserted-by":"publisher","first-page":"1391","DOI":"10.1111\/j.1478-3231.2012.02828.x","volume":"32","author":"TC Tan","year":"2012","unstructured":"Tan, T. C. et al. The serum hepcidin:ferritin ratio is a potential biomarker for cirrhosis. Liver Int. 32, 1391\u20131399 (2012).","journal-title":"Liver Int."},{"key":"BFncomms13817_CR39","doi-asserted-by":"publisher","first-page":"1141","DOI":"10.1093\/ndt\/gft467","volume":"29","author":"WH Horl","year":"2014","unstructured":"Horl, W. H. & Schmidt, A. Low hepcidin triggers hepatic iron accumulation in patients with hepatitis C. Nephrol. Dial. Transplant. 29, 1141\u20131144 (2014).","journal-title":"Nephrol. Dial. Transplant."},{"key":"BFncomms13817_CR40","doi-asserted-by":"publisher","first-page":"226","DOI":"10.1053\/j.gastro.2007.10.011","volume":"134","author":"S Nishina","year":"2008","unstructured":"Nishina, S. et al. Hepatitis C virus-induced reactive oxygen species raise hepatic iron level in mice by reducing hepcidin transcription. Gastroenterology 134, 226\u2013238 (2008).","journal-title":"Gastroenterology"},{"key":"BFncomms13817_CR41","doi-asserted-by":"publisher","first-page":"1979","DOI":"10.1002\/hep.21895","volume":"46","author":"DD Harrison-Findik","year":"2007","unstructured":"Harrison-Findik, D. D. et al. Iron-mediated regulation of liver hepcidin expression in rats and mice is abolished by alcohol. Hepatology 46, 1979\u20131985 (2007).","journal-title":"Hepatology"},{"key":"BFncomms13817_CR42","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1186\/1471-2407-8-167","volume":"8","author":"H Kijima","year":"2008","unstructured":"Kijima, H., Sawada, T., Tomosugi, N. & Kubota, K. Expression of hepcidin mRNA is uniformly suppressed in hepatocellular carcinoma. BMC Cancer 8, 167 (2008).","journal-title":"BMC Cancer"},{"key":"BFncomms13817_CR43","doi-asserted-by":"publisher","first-page":"240","DOI":"10.1038\/ki.2011.141","volume":"80","author":"DW Coyne","year":"2011","unstructured":"Coyne, D. W. Hepcidin: clinical utility as a diagnostic tool and therapeutic target. Kidney Int. 80, 240\u2013244 (2011).","journal-title":"Kidney Int."},{"key":"BFncomms13817_CR44","doi-asserted-by":"publisher","first-page":"1206","DOI":"10.1053\/j.gastro.2012.01.007","volume":"142","author":"CG Lee","year":"2012","unstructured":"Lee, C. G. et al. Farnesoid X receptor protects hepatocytes from injury by repressing miR-199a-3p, which increases levels of LKB1. Gastroenterology 142, 1206\u20131217.e7 (2012).","journal-title":"Gastroenterology"},{"key":"BFncomms13817_CR45","doi-asserted-by":"publisher","first-page":"360","DOI":"10.1038\/clpt.2010.89","volume":"88","author":"SG Kim","year":"2010","unstructured":"Kim, S. G. et al. Pharmacokinetics of oltipraz and its major metabolite (RM) in patients with liver fibrosis or cirrhosis: relationship with suppression of circulating TGF-beta1. Clin. Pharmacol. Ther. 88, 360\u2013368 (2010).","journal-title":"Clin. Pharmacol. Ther."},{"key":"BFncomms13817_CR46","doi-asserted-by":"publisher","first-page":"1425","DOI":"10.1172\/JCI119663","volume":"100","author":"J Wang","year":"1997","unstructured":"Wang, J. et al. Targeted overexpression of IGF-I evokes distinct patterns of organ remodeling in smooth muscle cell tissue beds of transgenic mice. J. Clin. Invest. 100, 1425\u20131439 (1997).","journal-title":"J. Clin. Invest."},{"key":"BFncomms13817_CR47","doi-asserted-by":"publisher","first-page":"2053","DOI":"10.1002\/hep.23931","volume":"52","author":"IJ Cho","year":"2010","unstructured":"Cho, I. J. et al. E-cadherin antagonizes transforming growth factor beta1 gene induction in hepatic stellate cells by inhibiting RhoA-dependent Smad3 phosphorylation. Hepatology 52, 2053\u20132064 (2010).","journal-title":"Hepatology"},{"key":"BFncomms13817_CR48","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1124\/mol.111.077149","volume":"82","author":"JH Koo","year":"2012","unstructured":"Koo, J. H., Lee, W. H., Lee, C. G. & Kim, S. G. Fyn inhibition by cycloalkane-fused 1,2-dithiole-3-thiones enhances antioxidant capacity and protects mitochondria from oxidative injury. Mol. Pharmacol. 82, 27\u201336 (2012).","journal-title":"Mol. Pharmacol."}],"container-title":["Nature Communications"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/ncomms13817.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/ncomms13817","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/ncomms13817.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,4]],"date-time":"2023-01-04T09:26:12Z","timestamp":1672824372000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/ncomms13817"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,12,22]]},"references-count":48,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2016,12,23]]}},"alternative-id":["BFncomms13817"],"URL":"https:\/\/doi.org\/10.1038\/ncomms13817","relation":{},"ISSN":["2041-1723"],"issn-type":[{"value":"2041-1723","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,12,22]]},"assertion":[{"value":"11 May 2016","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 November 2016","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 December 2016","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"S.R. is a consultant for Isis, Bayer A.G., Merganser Biotech and Novartis Pharmaceuticals. He also holds an equity\/ownership interest in Merganser Biotech and is a co-inventor for patents US8058061 B2 C12N 20111115 and US7541179 B2 C12N 20090602 about the generation of lentiviral vectors for the cure of hemoglobinopathies. The remaining authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"13817"}}