{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T21:25:35Z","timestamp":1784755535528,"version":"3.55.0"},"reference-count":49,"publisher":"Elsevier BV","issue":"11","license":[{"start":{"date-parts":[[2021,11,1]],"date-time":"2021-11-01T00:00:00Z","timestamp":1635724800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2021,11,1]],"date-time":"2021-11-01T00:00:00Z","timestamp":1635724800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2021,8,9]],"date-time":"2021-08-09T00:00:00Z","timestamp":1628467200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010573","name":"Stichting Dioraphte","doi-asserted-by":"publisher","award":["1115"],"award-info":[{"award-number":["1115"]}],"id":[{"id":"10.13039\/501100010573","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001826","name":"ZonMw","doi-asserted-by":"publisher","award":["40-00812-98-10054"],"award-info":[{"award-number":["40-00812-98-10054"]}],"id":[{"id":"10.13039\/501100001826","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease"],"published-print":{"date-parts":[[2021,11]]},"DOI":"10.1016\/j.bbadis.2021.166239","type":"journal-article","created":{"date-parts":[[2021,8,10]],"date-time":"2021-08-10T12:52:46Z","timestamp":1628599966000},"page":"166239","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":9,"title":["Inhibition of autotaxin by bile salts and bile salt-like molecules increases its expression by feedback regulation"],"prefix":"10.1016","volume":"1867","author":[{"given":"Jacqueline A.G.M.","family":"Langedijk","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dagmar","family":"Tolenaars","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth","family":"Bolier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-T\u00e9","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amber","family":"Meurs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Williamson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luciano","family":"Adorini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stan F.J.","family":"van de Graaf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrich","family":"Beuers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald Oude","family":"Elferink","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.bbadis.2021.166239_bb0005","doi-asserted-by":"crossref","DOI":"10.1053\/j.gastro.2010.05.009","article-title":"Lysophosphatidic acid is a potential mediator of cholestatic pruritus","volume":"139","author":"Kremer","year":"2010","journal-title":"Gastroenterology"},{"key":"10.1016\/j.bbadis.2021.166239_bb0010","doi-asserted-by":"crossref","first-page":"1391","DOI":"10.1002\/hep.25748","article-title":"Serum autotaxin is increased in pruritus of cholestasis, but not of other origin, and responds to therapeutic interventions","volume":"56","author":"Kremer","year":"2012","journal-title":"Hepatology"},{"key":"10.1016\/j.bbadis.2021.166239_bb0015","doi-asserted-by":"crossref","first-page":"1745","DOI":"10.1038\/jid.2014.24","article-title":"Serum autotaxin levels correlate with pruritus in patients with atopic dermatitis","volume":"134","author":"Nakao","year":"2014","journal-title":"J. Invest. Dermatol."},{"key":"10.1016\/j.bbadis.2021.166239_bb0020","doi-asserted-by":"crossref","first-page":"30847","DOI":"10.1038\/srep30847","article-title":"Serum autotaxin is a marker of the severity of liver injury and overall survival in patients with cholestatic liver diseases","volume":"6","author":"Wunsch","year":"2016","journal-title":"Sci. Rep."},{"key":"10.1016\/j.bbadis.2021.166239_bb0025","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1083\/jcb.200204026","article-title":"Autotaxin has lysophospholipase D activity leading to tumor cell growth and motility by lysophosphatidic acid production","volume":"158","author":"Umezu-Goto","year":"2002","journal-title":"J. Cell Biol."},{"key":"10.1016\/j.bbadis.2021.166239_bb0030","doi-asserted-by":"crossref","first-page":"39436","DOI":"10.1074\/jbc.M205623200","article-title":"Identification of human plasma lysophospholipase D, a lysophosphatidic acid-producing enzyme, as autotaxin, a multifunctional phosphodiesterase","volume":"277","author":"Tokumura","year":"2002","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.bbadis.2021.166239_bb0035","doi-asserted-by":"crossref","first-page":"5015","DOI":"10.1128\/MCB.02419-05","article-title":"Autotaxin, a secreted lysophospholipase D, is essential for blood vessel formation during development","volume":"26","author":"van Meeteren","year":"2006","journal-title":"Mol. Cell. Biol."},{"key":"10.1016\/j.bbadis.2021.166239_bb0040","doi-asserted-by":"crossref","first-page":"1192","DOI":"10.1194\/jlr.R046458","article-title":"LPA receptor signaling: pharmacology, physiology, and pathophysiology","volume":"55","author":"Yung","year":"2014","journal-title":"J. Lipid Res."},{"key":"10.1016\/j.bbadis.2021.166239_bb0045","doi-asserted-by":"crossref","first-page":"7776","DOI":"10.1074\/jbc.M708705200","article-title":"Murine and human autotaxin alpha, beta, and gamma isoforms: gene organization, tissue distribution, and biochemical characterization","volume":"283","author":"Giganti","year":"2008","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.bbadis.2021.166239_bb0050","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1016\/j.bbadis.2016.01.012","article-title":"Enteroendocrine cells are a potential source of serum autotaxin in men","volume":"1862","author":"Bolier","year":"2016","journal-title":"Biochim. Biophys. Acta"},{"key":"10.1016\/j.bbadis.2021.166239_bb0055","doi-asserted-by":"crossref","first-page":"1502","DOI":"10.1110\/ps.072819107","article-title":"Functional structure of the somatomedin B domain of vitronectin","volume":"16","author":"Zhou","year":"2007","journal-title":"Protein Sci."},{"key":"10.1016\/j.bbadis.2021.166239_bb0060","doi-asserted-by":"crossref","first-page":"14296","DOI":"10.1074\/jbc.M900790200","article-title":"Domain interplay mediated by an essential disulfide linkage is critical for the activity and secretion of the metastasis-promoting enzyme autotaxin","volume":"284","author":"Jansen","year":"2009","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.bbadis.2021.166239_bb0065","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1038\/nsmb.1998","article-title":"Crystal structure of autotaxin and insight into GPCR activation by lipid mediators","volume":"18","author":"Nishimasu","year":"2011","journal-title":"Nat. Struct. Mol. Biol."},{"key":"10.1016\/j.bbadis.2021.166239_bb0070","doi-asserted-by":"crossref","first-page":"11248","DOI":"10.1038\/ncomms11248","article-title":"Steroid binding to Autotaxin links bile salts and lysophosphatidic acid signalling","volume":"7","author":"Keune","year":"2016","journal-title":"Nat. Commun."},{"key":"10.1016\/j.bbadis.2021.166239_bb0075","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1152\/physrev.00027.2002","article-title":"Bile salt transporters: molecular characterization, function, and regulation","volume":"83","author":"Trauner","year":"2003","journal-title":"Physiol. Rev."},{"key":"10.1016\/j.bbadis.2021.166239_bb0080","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1002\/hep.21271","article-title":"Biliary drainage transiently relieves intractable pruritus in primary biliary cirrhosis","volume":"44","author":"Beuers","year":"2006","journal-title":"Hepatology"},{"key":"10.1016\/j.bbadis.2021.166239_bb0085","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1172\/JCI117658","article-title":"Regulation of biliary lipid secretion by mdr2 P-glycoprotein in the mouse","volume":"95","author":"Oude Elferink","year":"1995","journal-title":"J. Clin. Invest."},{"key":"10.1016\/j.bbadis.2021.166239_bb0090","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1016\/S0022-2275(20)40709-6","article-title":"Re-evaluation of the 3 alpha-hydroxysteroid dehydrogenase assay for total bile acids in bile","volume":"19","author":"Turley","year":"1978","journal-title":"J. Lipid Res."},{"key":"10.1016\/j.bbadis.2021.166239_bb0095","doi-asserted-by":"crossref","first-page":"43214","DOI":"10.1074\/jbc.M306709200","article-title":"Lipid phosphate phosphatases regulate lysophosphatidic acid production and signaling in platelets: studies using chemical inhibitors of lipid phosphate phosphatase activity","volume":"278","author":"Smyth","year":"2003","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.bbadis.2021.166239_bb0100","doi-asserted-by":"crossref","first-page":"1357","DOI":"10.1042\/BST0331357","article-title":"New metabolically stabilized analogues of lysophosphatidic acid: agonists, antagonists and enzyme inhibitors","volume":"33","author":"Prestwich","year":"2005","journal-title":"Biochem. Soc. Trans."},{"key":"10.1016\/j.bbadis.2021.166239_bb0105","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1042\/BJ20041160","article-title":"Lipid phosphate phosphatase-1 regulates lysophosphatidic acid-induced calcium release, NF-kappaB activation and interleukin-8 secretion in human bronchial epithelial cells","volume":"385","author":"Zhao","year":"2005","journal-title":"Biochem. J."},{"key":"10.1016\/j.bbadis.2021.166239_bb0110","doi-asserted-by":"crossref","first-page":"5323","DOI":"10.1016\/j.bmcl.2004.08.019","article-title":"Alkyl lysophosphatidic acid and fluoromethylene phosphonate analogs as metabolically-stabilized agonists for LPA receptors","volume":"14","author":"Xu","year":"2004","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"10.1016\/j.bbadis.2021.166239_bb0115","doi-asserted-by":"crossref","first-page":"34654","DOI":"10.1074\/jbc.M111.276725","article-title":"Binding of autotaxin to integrins localizes lysophosphatidic acid production to platelets and mammalian cells","volume":"286","author":"Fulkerson","year":"2011","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.bbadis.2021.166239_bb0120","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1186\/1476-4598-9-71","article-title":"Autotaxin expression and its connection with the TNF-alpha-NF-kappaB axis in human hepatocellular carcinoma","volume":"9","author":"Wu","year":"2010","journal-title":"Mol. Cancer"},{"key":"10.1016\/j.bbadis.2021.166239_bb0125","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1084\/jem.20112012","article-title":"Autotaxin expression from synovial fibroblasts is essential for the pathogenesis of modeled arthritis","volume":"209","author":"Nikitopoulou","year":"2012","journal-title":"J. Exp. Med."},{"key":"10.1016\/j.bbadis.2021.166239_bb0130","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1136\/gut.17.11.861","article-title":"Sulphated and unsulphated bile acids in serum, bile, and urine of patients with cholestasis","volume":"17","author":"van Berge Henegouwen","year":"1976","journal-title":"Gut"},{"key":"10.1016\/j.bbadis.2021.166239_bb0135","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1093\/toxsci\/kfn268","article-title":"Bile acid sulfation: a pathway of bile acid elimination and detoxification","volume":"108","author":"Alnouti","year":"2009","journal-title":"Toxicol. Sci."},{"key":"10.1016\/j.bbadis.2021.166239_bb0140","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1002\/hep.1840050325","article-title":"Biliary and urinary excretion of sulfated, glucuronidated and tetrahydroxylated bile acids in cirrhotic patients","volume":"5","author":"Stiehl","year":"1985","journal-title":"Hepatology"},{"key":"10.1016\/j.bbadis.2021.166239_bb0145","doi-asserted-by":"crossref","first-page":"1287","DOI":"10.1002\/hep.28265","article-title":"Prognostic and mechanistic potential of progesterone sulfates in intrahepatic cholestasis of pregnancy and pruritus gravidarum","volume":"63","author":"Abu-Hayyeh","year":"2016","journal-title":"Hepatology"},{"key":"10.1016\/j.bbadis.2021.166239_bb0150","doi-asserted-by":"crossref","first-page":"16504","DOI":"10.1074\/jbc.M109.072140","article-title":"Inhibition of Na+-taurocholate Co-transporting polypeptide-mediated bile acid transport by cholestatic sulfated progesterone metabolites","volume":"285","author":"Abu-Hayyeh","year":"2010","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.bbadis.2021.166239_bb0155","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1002\/hep.26055","article-title":"Intrahepatic cholestasis of pregnancy levels of sulfated progesterone metabolites inhibit farnesoid X receptor resulting in a cholestatic phenotype","volume":"57","author":"Abu-Hayyeh","year":"2013","journal-title":"Hepatology"},{"key":"10.1016\/j.bbadis.2021.166239_bb0160","first-page":"134","article-title":"Clinical and biochemical findings in progressive familial intrahepatic cholestasis","volume":"18","author":"Whitington","year":"1994","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"10.1016\/j.bbadis.2021.166239_bb0165","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1053\/jhep.2001.22646","article-title":"Hepatobiliary transporter expression in percutaneous liver biopsies of patients with cholestatic liver diseases","volume":"33","author":"Zollner","year":"2001","journal-title":"Hepatology"},{"key":"10.1016\/j.bbadis.2021.166239_bb0170","unstructured":"https:\/\/www.prestwickchemical.com\/screening-libraries\/prestwick-chemical-library\/. Prestwick chemical library: 1520 FDA-approved & EMA appoved drugs for HTS and HCS screening."},{"key":"10.1016\/j.bbadis.2021.166239_bb0175","doi-asserted-by":"crossref","first-page":"2184","DOI":"10.1016\/S0140-6736(19)33041-7","article-title":"Obeticholic acid for the treatment of non-alcoholic steatohepatitis: interim analysis from a multicentre, randomised, placebo-controlled phase 3 trial","volume":"394","author":"Younossi","year":"2019","journal-title":"Lancet"},{"key":"10.1016\/j.bbadis.2021.166239_bb0180","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1016\/S2468-1253(19)30094-9","article-title":"Long-term efficacy and safety of obeticholic acid for patients with primary biliary cholangitis: 3-year results of an international open-label extension study","volume":"4","author":"Trauner","year":"2019","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"10.1016\/j.bbadis.2021.166239_bb0185","doi-asserted-by":"crossref","first-page":"1890","DOI":"10.1002\/hep.29569","article-title":"A randomized trial of obeticholic acid monotherapy in patients with primary biliary cholangitis","volume":"67","author":"Kowdley","year":"2018","journal-title":"Hepatology"},{"key":"10.1016\/j.bbadis.2021.166239_bb0190","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1111\/apt.14492","article-title":"Clinical and metabolic effects associated with weight changes and obeticholic acid in non-alcoholic steatohepatitis","volume":"47","author":"Hameed","year":"2018","journal-title":"Aliment. Pharmacol. Ther."},{"key":"10.1016\/j.bbadis.2021.166239_bb0195","doi-asserted-by":"crossref","first-page":"1134","DOI":"10.1194\/jlr.M057661","article-title":"Regulation of autotaxin expression and secretion by lysophosphatidate and sphingosine 1-phosphate","volume":"56","author":"Benesch","year":"2015","journal-title":"J. Lipid Res."},{"key":"10.1016\/j.bbadis.2021.166239_bb0200","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1042\/BJ20081888","article-title":"Lipid phosphate phosphohydrolase type 1 (LPP1) degrades extracellular lysophosphatidic acid in vivo","volume":"419","author":"Tomsig","year":"2009","journal-title":"Biochem. J."},{"key":"10.1016\/j.bbadis.2021.166239_bb0205","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1194\/jlr.M065086","article-title":"Tetracyclines increase lipid phosphate phosphatase expression on plasma membranes and turnover of plasma lysophosphatidate","volume":"57","author":"Tang","year":"2016","journal-title":"J. Lipid Res."},{"key":"10.1016\/j.bbadis.2021.166239_bb0210","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1042\/EBC20190088","article-title":"Signalling by lysophosphatidate and its health implications","volume":"64","author":"Hemmings","year":"2020","journal-title":"Essays Biochem."},{"key":"10.1016\/j.bbadis.2021.166239_bb0215","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1046\/j.1440-1746.2002.02672.x","article-title":"Tumor necrosis factor-alpha and transforming growth factor-beta reflect severity of liver damage in primary biliary cirrhosis","volume":"17","author":"Neuman","year":"2002","journal-title":"J. Gastroenterol. Hepatol."},{"key":"10.1016\/j.bbadis.2021.166239_bb0220","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.3748\/wjg.v24.i11.1239","article-title":"Serum autotaxin levels are correlated with hepatic fibrosis and ballooning in patients with non-alcoholic fatty liver disease","volume":"24","author":"Fujimori","year":"2018","journal-title":"World J. Gastroenterol."},{"key":"10.1016\/j.bbadis.2021.166239_bb0225","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1111\/hepr.12997","article-title":"Serum autotaxin is a useful liver fibrosis marker in patients with chronic hepatitis B virus infection","volume":"48","author":"Joshita","year":"2018","journal-title":"Hepatol. Res."},{"key":"10.1016\/j.bbadis.2021.166239_bb0230","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1177\/0004563217741509","article-title":"Performance of autotaxin as a serum marker for liver fibrosis","volume":"55","author":"Ikeda","year":"2018","journal-title":"Ann. Clin. Biochem."},{"key":"10.1016\/j.bbadis.2021.166239_bb0235","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1097\/01.mcg.0000225642.90898.0e","article-title":"Both plasma lysophosphatidic acid and serum autotaxin levels are increased in chronic hepatitis C","volume":"41","author":"Watanabe","year":"2007","journal-title":"J. Clin. Gastroenterol."},{"key":"10.1016\/j.bbadis.2021.166239_bb0240","doi-asserted-by":"crossref","first-page":"1386","DOI":"10.1095\/biolreprod.102.004051","article-title":"Increased production of bioactive lysophosphatidic acid by serum lysophospholipase D in human pregnancy","volume":"67","author":"Tokumura","year":"2002","journal-title":"Biol. Reprod."},{"key":"10.1016\/j.bbadis.2021.166239_bb0245","doi-asserted-by":"crossref","first-page":"6127","DOI":"10.1038\/s41598-021-85660-1","article-title":"Reduced spontaneous itch in mouse models of cholestasis","volume":"11","author":"Langedijk","year":"2021","journal-title":"Sci. Rep."}],"container-title":["Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0925443921001721?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0925443921001721?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T14:44:58Z","timestamp":1778769898000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0925443921001721"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11]]},"references-count":49,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2021,11]]}},"alternative-id":["S0925443921001721"],"URL":"https:\/\/doi.org\/10.1016\/j.bbadis.2021.166239","relation":{},"ISSN":["0925-4439"],"issn-type":[{"value":"0925-4439","type":"print"}],"subject":[],"published":{"date-parts":[[2021,11]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Inhibition of autotaxin by bile salts and bile salt-like molecules increases its expression by feedback regulation","name":"articletitle","label":"Article Title"},{"value":"Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.bbadis.2021.166239","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2021 Amsterdam UMC, Amsterdam, The Netherlands. Published by Elsevier B.V.","name":"copyright","label":"Copyright"}],"article-number":"166239"}}