{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T00:09:56Z","timestamp":1771891796608,"version":"3.50.1"},"reference-count":36,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2020,1,8]],"date-time":"2020-01-08T00:00:00Z","timestamp":1578441600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2020,1,8]],"date-time":"2020-01-08T00:00:00Z","timestamp":1578441600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Pharmacol. Rep"],"published-print":{"date-parts":[[2020,8]]},"DOI":"10.1007\/s43440-019-00043-8","type":"journal-article","created":{"date-parts":[[2020,1,8]],"date-time":"2020-01-08T14:02:50Z","timestamp":1578492170000},"page":"935-944","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Therapeutic action against chronic cholestatic liver injury by low-dose fenofibrate involves anti-chemotaxis via JNK\u2013AP1\u2013CCL2\/CXCL2 signaling"],"prefix":"10.1007","volume":"72","author":[{"given":"Manyun","family":"Dai","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julin","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yishuang","family":"Luo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liping","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haoyue","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gangming","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aiming","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2020,1,8]]},"reference":[{"issue":"5","key":"43_CR1","doi-asserted-by":"publisher","first-page":"1481","DOI":"10.1053\/j.gastro.2010.09.004","volume":"139","author":"GM Hirschfield","year":"2010","unstructured":"Hirschfield GM, Heathcote EJ, Gershwin ME. Pathogenesis of cholestatic liver disease and therapeutic approaches. Gastroenterology. 2010;139(5):1481\u201396.","journal-title":"Gastroenterology"},{"issue":"2","key":"43_CR2","doi-asserted-by":"publisher","first-page":"571","DOI":"10.1002\/hep.23678","volume":"52","author":"B Lindkvist","year":"2010","unstructured":"Lindkvist B, Benito de Valle M, Gullberg B, Bjornsson E. Incidence and prevalence of primary sclerosing cholangitis in a defined adult population in Sweden. Hepatology. 2010;52(2):571\u20137.","journal-title":"Hepatology"},{"issue":"5","key":"43_CR3","doi-asserted-by":"publisher","first-page":"1590","DOI":"10.1002\/hep.24247","volume":"53","author":"NA Molodecky","year":"2011","unstructured":"Molodecky NA, Kareemi H, Parab R, Barkema HW, Quan H, Myers RP, et al. Incidence of primary sclerosing cholangitis: a systematic review and meta-analysis. Hepatology. 2011;53(5):1590\u20139.","journal-title":"Hepatology"},{"issue":"9904","key":"43_CR4","doi-asserted-by":"publisher","first-page":"1587","DOI":"10.1016\/S0140-6736(13)60096-3","volume":"382","author":"GM Hirschfield","year":"2013","unstructured":"Hirschfield GM, Karlsen TH, Lindor KD, Adams DH. Primary sclerosing cholangitis. Lancet. 2013;382(9904):1587\u201399.","journal-title":"Lancet"},{"key":"43_CR5","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1186\/1471-230X-10-100","volume":"10","author":"H Liu","year":"2010","unstructured":"Liu H, Liu Y, Wang L, Xu D, Lin B, Zhong R, et al. Prevalence of primary biliary cirrhosis in adults referring hospital for annual health check-up in Southern China. BMC Gastroenterol. 2010;10:100.","journal-title":"BMC Gastroenterol"},{"issue":"5","key":"43_CR6","doi-asserted-by":"publisher","first-page":"1181","DOI":"10.1016\/j.jhep.2011.10.025","volume":"56","author":"K Boonstra","year":"2012","unstructured":"Boonstra K, Beuers U, Ponsioen CY. Epidemiology of primary sclerosing cholangitis and primary biliary cirrhosis: a systematic review. J Hepatol. 2012;56(5):1181\u20138.","journal-title":"J Hepatol"},{"issue":"4","key":"43_CR7","doi-asserted-by":"publisher","first-page":"610","DOI":"10.1136\/gut.38.4.610","volume":"38","author":"U Broome","year":"1996","unstructured":"Broome U, Olsson R, Loof L, Bodemar G, Hultcrantz R, Danielsson A, et al. Natural history and prognostic factors in 305 Swedish patients with primary sclerosing cholangitis. Gut. 1996;38(4):610\u20135.","journal-title":"Gut"},{"issue":"3","key":"43_CR8","doi-asserted-by":"publisher","first-page":"560","DOI":"10.1053\/j.gastro.2012.12.005","volume":"144","author":"M Carbone","year":"2013","unstructured":"Carbone M, Mells GF, Pells G, Dawwas MF, Newton JL, Heneghan MA, et al. Sex and age are determinants of the clinical phenotype of primary biliary cirrhosis and response to ursodeoxycholic acid. Gastroenterology. 2013;144(3):560\u20139.","journal-title":"Gastroenterology"},{"issue":"2","key":"43_CR9","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1111\/j.1365-2036.2010.04512.x","volume":"33","author":"C Levy","year":"2011","unstructured":"Levy C, Peter JA, Nelson DR, Keach J, Petz J, Cabrera R, et al. Pilot study: fenofibrate for patients with primary biliary cirrhosis and an incomplete response to ursodeoxycholic acid. Aliment Pharmacol Ther. 2011;33(2):235\u201342.","journal-title":"Aliment Pharmacol Ther"},{"issue":"2","key":"43_CR10","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1111\/apt.13465","volume":"43","author":"AC Cheung","year":"2016","unstructured":"Cheung AC, Lapointe-Shaw L, Kowgier M, Meza-Cardona J, Hirschfield GM, Janssen HL, et al. Combined ursodeoxycholic acid (UDCA) and fenofibrate in primary biliary cholangitis patients with incomplete UDCA response may improve outcomes. Aliment Pharmacol Ther. 2016;43(2):283\u201393.","journal-title":"Aliment Pharmacol Ther"},{"key":"43_CR11","doi-asserted-by":"publisher","first-page":"781348","DOI":"10.1155\/2013\/781348","volume":"2013","author":"A El-Sisi","year":"2013","unstructured":"El-Sisi A, Hegazy S, El-Khateeb E. Effects of three different fibrates on intrahepatic cholestasis experimentally induced in rats. PPAR Res. 2013;2013:781348.","journal-title":"PPAR Res"},{"issue":"1","key":"43_CR12","doi-asserted-by":"publisher","first-page":"9967","DOI":"10.1038\/s41598-017-10524-6","volume":"7","author":"Q Zhao","year":"2017","unstructured":"Zhao Q, Yang R, Wang J, Hu DD, Li F. PPARalpha activation protects against cholestatic liver injury. Sci Rep. 2017;7(1):9967.","journal-title":"Sci Rep"},{"issue":"3","key":"43_CR13","doi-asserted-by":"publisher","first-page":"339","DOI":"10.2131\/jts.41.339","volume":"41","author":"P Thongnuanjan","year":"2016","unstructured":"Thongnuanjan P, Soodvilai S, Chatsudthipong V, Soodvilai S. Fenofibrate reduces cisplatin-induced apoptosis of renal proximal tubular cells via inhibition of JNK and p38 pathways. J Toxicol Sci. 2016;41(3):339\u201349.","journal-title":"J Toxicol Sci"},{"issue":"4","key":"43_CR14","doi-asserted-by":"publisher","first-page":"603","DOI":"10.3945\/jn.110.135210","volume":"141","author":"MA Abdelmegeed","year":"2011","unstructured":"Abdelmegeed MA, Yoo SH, Henderson LE, Gonzalez FJ, Woodcroft KJ, Song BJ. PPARalpha expression protects male mice from high fat-induced nonalcoholic fatty liver. J Nutr. 2011;141(4):603\u201310.","journal-title":"J Nutr"},{"issue":"18","key":"43_CR15","doi-asserted-by":"publisher","first-page":"3000","DOI":"10.1111\/bph.13928","volume":"174","author":"M Dai","year":"2017","unstructured":"Dai M, Yang J, Xie M, Lin J, Luo M, Hua H, et al. Inhibition of JNK signalling mediates PPARalpha-dependent protection against intrahepatic cholestasis by fenofibrate. Br J Pharmacol. 2017;174(18):3000\u201317.","journal-title":"Br J Pharmacol"},{"issue":"1","key":"43_CR16","first-page":"50","volume":"32","author":"AA El-Faramawy","year":"2011","unstructured":"El-Faramawy AA, El-Shazly LB, Abbass AA, Ismail HA. Serum IL-6 and IL-8 in infants with biliary atresia in comparison to intrahepatic cholestasis. Trop Gastroenterol. 2011;32(1):50\u20135.","journal-title":"Trop Gastroenterol"},{"issue":"1","key":"43_CR17","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1016\/j.ajpath.2010.11.026","volume":"178","author":"K Allen","year":"2011","unstructured":"Allen K, Jaeschke H, Copple BL. Bile acids induce inflammatory genes in hepatocytes: a novel mechanism of inflammation during obstructive cholestasis. Am J Pathol. 2011;178(1):175\u201386.","journal-title":"Am J Pathol"},{"issue":"5","key":"43_CR18","doi-asserted-by":"publisher","first-page":"e90780","DOI":"10.1172\/jci.insight.90780","volume":"2","author":"SY Cai","year":"2017","unstructured":"Cai SY, Ouyang X, Chen Y, Soroka CJ, Wang J, Mennone A, et al. Bile acids initiate cholestatic liver injury by triggering a hepatocyte-specific inflammatory response. JCI Insight. 2017;2(5):e90780.","journal-title":"JCI Insight"},{"issue":"6","key":"43_CR19","doi-asserted-by":"publisher","first-page":"3012","DOI":"10.1128\/MCB.15.6.3012","volume":"15","author":"SS Lee","year":"1995","unstructured":"Lee SS, Pineau T, Drago J, Lee EJ, Owens JW, Kroetz DL, et al. Targeted disruption of the alpha isoform of the peroxisome proliferator-activated receptor gene in mice results in abolishment of the pleiotropic effects of peroxisome proliferators. Mol Cell Biol. 1995;15(6):3012\u201322.","journal-title":"Mol Cell Biol"},{"issue":"3","key":"43_CR20","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1124\/jpet.113.210880","volume":"349","author":"N Joshi","year":"2014","unstructured":"Joshi N, Kopec AK, Towery K, Williams KJ, Luyendyk JP. The antifibrinolytic drug tranexamic acid reduces liver injury and fibrosis in a mouse model of chronic bile duct injury. J Pharmacol Exp Ther. 2014;349(3):383\u201392.","journal-title":"J Pharmacol Exp Ther"},{"issue":"2","key":"43_CR21","doi-asserted-by":"publisher","first-page":"897","DOI":"10.1007\/s00204-016-1779-7","volume":"91","author":"M Luo","year":"2017","unstructured":"Luo M, Tan Z, Dai M, Song D, Lin J, Xie M, et al. Dual action of peroxisome proliferator-activated receptor alpha in perfluorodecanoic acid-induced hepatotoxicity. Arch Toxicol. 2017;91(2):897\u2013907.","journal-title":"Arch Toxicol"},{"issue":"9","key":"43_CR22","doi-asserted-by":"publisher","first-page":"1203","DOI":"10.1111\/jphp.12592","volume":"68","author":"Z Tan","year":"2016","unstructured":"Tan Z, Luo M, Yang J, Cheng Y, Huang J, Lu C, et al. Chlorogenic acid inhibits cholestatic liver injury induced by alpha-naphthylisothiocyanate: involvement of STAT3 and NFkappaB signalling regulation. J Pharm Pharmacol. 2016;68(9):1203\u201313.","journal-title":"J Pharm Pharmacol"},{"key":"43_CR23","doi-asserted-by":"publisher","first-page":"120","DOI":"10.2174\/1874192401004010120","volume":"4","author":"EN Liberopoulos","year":"2010","unstructured":"Liberopoulos EN, Florentin M, Elisaf MS, Mikhailidis DP, Tsianos E. Fenofibrate in primary biliary cirrhosis: a pilot study. Open Cardiovasc Med J. 2010;4:120\u20136.","journal-title":"Open Cardiovasc Med J"},{"issue":"5","key":"43_CR24","doi-asserted-by":"publisher","first-page":"489","DOI":"10.3109\/0886022X.2011.577545","volume":"33","author":"CC Liang","year":"2011","unstructured":"Liang CC, Wang IK, Kuo HL, Yeh HC, Lin HH, Liu YL, et al. Long-term use of fenofibrate is associated with increased prevalence of gallstone disease among patients undergoing maintenance hemodialysis. Ren Fail. 2011;33(5):489\u201393.","journal-title":"Ren Fail"},{"issue":"4","key":"43_CR25","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1021\/mp0499656","volume":"1","author":"T Maeda","year":"2004","unstructured":"Maeda T, Miyata M, Yotsumoto T, Kobayashi D, Nozawa T, Toyama K, et al. Regulation of drug transporters by the farnesoid X receptor in mice. Mol Pharm. 2004;1(4):281\u20139.","journal-title":"Mol Pharm"},{"issue":"3","key":"43_CR26","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1159\/000450908","volume":"35","author":"FJ Gonzalez","year":"2017","unstructured":"Gonzalez FJ, Jiang C, Xie C, Patterson AD. Intestinal farnesoid X receptor signaling modulates metabolic disease. Dig Dis. 2017;35(3):178\u201384.","journal-title":"Dig Dis"},{"key":"43_CR27","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1016\/j.tox.2017.05.012","volume":"386","author":"H Wang","year":"2017","unstructured":"Wang H, Fang ZZ, Meng R, Cao YF, Tanaka N, Krausz KW, et al. Glycyrrhizin and glycyrrhetinic acid inhibits alpha-naphthyl isothiocyanate-induced liver injury and bile acid cycle disruption. Toxicology. 2017;386:133\u201342.","journal-title":"Toxicology"},{"issue":"19","key":"43_CR28","doi-asserted-by":"publisher","first-page":"15816","DOI":"10.1074\/jbc.M010878200","volume":"276","author":"S Gupta","year":"2001","unstructured":"Gupta S, Stravitz RT, Dent P, Hylemon PB. Down-regulation of cholesterol 7alpha-hydroxylase (CYP7A1) gene expression by bile acids in primary rat hepatocytes is mediated by the c-Jun N-terminal kinase pathway. J Biol Chem. 2001;276(19):15816\u201322.","journal-title":"J Biol Chem"},{"issue":"3","key":"43_CR29","doi-asserted-by":"publisher","first-page":"1030","DOI":"10.1002\/hep.26894","volume":"59","author":"NS Ghonem","year":"2014","unstructured":"Ghonem NS, Ananthanarayanan M, Soroka CJ, Boyer JL. Peroxisome proliferator-activated receptor alpha activates human multidrug resistance transporter 3\/ATP-binding cassette protein subfamily B4 transcription and increases rat biliary phosphatidylcholine secretion. Hepatology. 2014;59(3):1030\u201342.","journal-title":"Hepatology"},{"issue":"12","key":"43_CR30","doi-asserted-by":"publisher","first-page":"855","DOI":"10.1007\/s00228-003-0704-1","volume":"59","author":"N Roglans","year":"2004","unstructured":"Roglans N, Vazquez-Carrera M, Alegret M, Novell F, Zambon D, Ros E, et al. Fibrates modify the expression of key factors involved in bile-acid synthesis and biliary-lipid secretion in gallstone patients. Eur J Clin Pharmacol. 2004;59(12):855\u201361.","journal-title":"Eur J Clin Pharmacol"},{"issue":"1","key":"43_CR31","doi-asserted-by":"publisher","first-page":"468","DOI":"10.3390\/ijms15010468","volume":"15","author":"MM Lay","year":"2014","unstructured":"Lay MM, Karsani SA, Malek SN. 1-(2,6-dihydroxy-4-methoxyphenyl)-2-(4-hydroxyphenyl) ethanone-induced cell cycle arrest in G(1)\/G(0) in HT-29 cells human colon adenocarcinoma cells. Int J Mol Sci. 2014;15(1):468\u201383.","journal-title":"Int J Mol Sci"},{"issue":"4","key":"43_CR32","doi-asserted-by":"publisher","first-page":"1500","DOI":"10.1021\/acs.jproteome.7b00838","volume":"17","author":"M Dai","year":"2018","unstructured":"Dai M, Hua H, Lin H, Xu G, Hu X, Li F, et al. Targeted metabolomics reveals a protective role for basal PPAR\u03b1 in cholestasis induced by \u03b1-Naphthylisothiocyanate. J Proteome Res. 2018;17(4):1500\u20138.","journal-title":"J Proteome Res"},{"key":"43_CR33","doi-asserted-by":"publisher","first-page":"3180396","DOI":"10.1155\/2018\/3180396","volume":"2018","author":"W Wang","year":"2018","unstructured":"Wang W, Chen K, Xia Y, Mo W, Wang F, Dai W, et al. The hepatoprotection by oleanolic acid preconditioning: focusing on PPAR\u03b1 activation. PPAR Res. 2018;2018:3180396.","journal-title":"PPAR Res"},{"issue":"5196","key":"43_CR34","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1126\/science.7824938","volume":"267","author":"S Gupta","year":"1995","unstructured":"Gupta S, Campbell D, Derijard B, Davis RJ. Transcription factor ATF2 regulation by the JNK signal transduction pathway. Science. 1995;267(5196):389\u201393.","journal-title":"Science"},{"issue":"1","key":"43_CR35","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1016\/j.nbd.2008.12.007","volume":"34","author":"V Vukic","year":"2009","unstructured":"Vukic V, Callaghan D, Walker D, Lue LF, Liu QY, Couraud PO, et al. Expression of inflammatory genes induced by beta-amyloid peptides in human brain endothelial cells and in Alzheimer\u2019s brain is mediated by the JNK\u2013AP1 signaling pathway. Neurobiol Dis. 2009;34(1):95\u2013106.","journal-title":"Neurobiol Dis"},{"key":"43_CR36","doi-asserted-by":"publisher","first-page":"899","DOI":"10.2741\/A887","volume":"7","author":"F Marra","year":"2002","unstructured":"Marra F. Chemokines in liver inflammation and fibrosis. Front Biosci. 2002;7:899\u2013914.","journal-title":"Front Biosci"}],"container-title":["Pharmacological Reports"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s43440-019-00043-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1007\/s43440-019-00043-8\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s43440-019-00043-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,1,7]],"date-time":"2021-01-07T00:35:06Z","timestamp":1609979706000},"score":1,"resource":{"primary":{"URL":"http:\/\/link.springer.com\/10.1007\/s43440-019-00043-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,1,8]]},"references-count":36,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2020,8]]}},"alternative-id":["43"],"URL":"https:\/\/doi.org\/10.1007\/s43440-019-00043-8","relation":{},"ISSN":["1734-1140","2299-5684"],"issn-type":[{"value":"1734-1140","type":"print"},{"value":"2299-5684","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,1,8]]},"assertion":[{"value":"21 July 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 October 2019","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 November 2019","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 January 2020","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with ethical standards"}},{"value":"There are no conflict of interests to be declared by the authors in this work.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}