{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T22:43:01Z","timestamp":1773960181848,"version":"3.50.1"},"reference-count":98,"publisher":"Georg Thieme Verlag KG","issue":"03","funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health Grant","doi-asserted-by":"crossref","award":["R01DK132781"],"award-info":[{"award-number":["R01DK132781"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100011475","name":"Cholangiocarcinoma Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100011475","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100001172","name":"The Hormel Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100001172","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Semin Liver Dis"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:p>Primary cilia, hair-like projections on the surface of various cell types, play crucial roles in sensing and regulating environmental cues within the liver, particularly among cholangiocytes. These structures detect changes in bile composition, flow, and other biochemical signals, integrating this information to modulate cellular processes. Dysfunction in cholangiocyte cilia\u2014whether due to structural abnormalities or genetic mutations\u2014has been linked to an array of cholangiopathies and ciliopathies. These include conditions such as biliary atresia, cholangiocarcinoma, primary sclerosing cholangitis, and polycystic liver diseases, each with distinct clinical phenotypes influenced by impaired ciliary function. Given the complexity of the ciliary proteome and its role in cellular signaling, including the Hedgehog, Wnt, and TGR5 pathways, ciliary dysfunction disrupts essential signaling cascades, thus driving disease progression. While over 40 gene mutations are associated with ciliopathic features, there may be additional contributors within the expansive ciliary proteome. This study synthesizes current knowledge on cholangiocyte cilia, emphasizing their mechanistic role in liver disease, and highlights emerging therapeutic strategies aimed at restoring ciliary function. In conclusion, ciliotherapies are proposed as a promising approach for addressing cholangiopathies, with the potential to shift the current therapeutic landscape.<\/jats:p>","DOI":"10.1055\/a-2563-9791","type":"journal-article","created":{"date-parts":[[2025,3,21]],"date-time":"2025-03-21T20:26:21Z","timestamp":1742588781000},"page":"348-361","source":"Crossref","is-referenced-by-count":2,"title":["Primary Cilia in Hepatic Biliary Hyperplasia: Implications for Liver Diseases"],"prefix":"10.1055","volume":"45","author":[{"given":"Kishor","family":"Pant","sequence":"additional","affiliation":[{"name":"The Hormel Institute, University of Minnesota, Austin, Minnesota"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Estanislao","family":"Peixoto","sequence":"additional","affiliation":[{"name":"The Hormel Institute, University of Minnesota, Austin, Minnesota"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sergio A.","family":"Gradilone","sequence":"additional","affiliation":[{"name":"The Hormel Institute, University of Minnesota, Austin, Minnesota"},{"name":"Masonic Cancer Centre, University of Minnesota, Minneapolis, Minnesota"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"194","published-online":{"date-parts":[[2025,4,25]]},"reference":[{"issue":"35","key":"ref1","doi-asserted-by":"crossref","first-page":"12871","DOI":"10.1073\/pnas.1323292111","article-title":"Primary cilia signaling mediates intraocular pressure sensation","volume":"111","author":"N Luo","year":"2014","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"04","key":"ref2","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1038\/s41581-019-0116-9","article-title":"Cellular signalling by primary cilia in development, organ function and disease","volume":"15","author":"Z Anvarian","year":"2019","journal-title":"Nat Rev Nephrol"},{"issue":"07","key":"ref3","doi-asserted-by":"crossref","first-page":"14","DOI":"10.3390\/genes14071428","article-title":"Cilia and cancer: from molecular genetics to therapeutic strategies","volume":"14","author":"P Carotenuto","year":"2023","journal-title":"Genes (Basel)"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"113906","DOI":"10.1016\/j.bcp.2020.113906","article-title":"The primary cilium: Its role as a tumor suppressor organelle","volume":"175","author":"E Peixoto","year":"2020","journal-title":"Biochem Pharmacol"},{"issue":"02","key":"ref5","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1002\/hep.29832","article-title":"MicroRNA (miR)-433 and miR-22 dysregulations induce histone-deacetylase-6 overexpression and ciliary loss in cholangiocarcinoma","volume":"68","author":"A P Mansini","year":"2018","journal-title":"Hepatology"},{"issue":"01","key":"ref6","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1159\/000324121","article-title":"The role of cilia in the regulation of bile flow","volume":"29","author":"N F Larusso","year":"2011","journal-title":"Dig Dis"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"8","DOI":"10.3389\/fcell.2018.00008","article-title":"Signaling through the primary cilium","volume":"6","author":"G Wheway","year":"2018","journal-title":"Front Cell Dev Biol"},{"issue":"07","key":"ref8","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1038\/s41580-023-00698-5","article-title":"Emerging mechanistic understanding of cilia function in cellular signalling","volume":"25","author":"K I Hilgendorf","year":"2024","journal-title":"Nat Rev Mol Cell Biol"},{"issue":"04","key":"ref9","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1038\/s41422-023-00778-3","article-title":"Human IFT-A complex structures provide molecular insights into ciliary transport","volume":"33","author":"M Jiang","year":"2023","journal-title":"Cell Res"},{"issue":"03","key":"ref10","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1053\/j.gastro.2006.07.003","article-title":"Cholangiocyte cilia detect changes in luminal fluid flow and transmit them into intracellular Ca2+ and cAMP signaling","volume":"131","author":"A I Masyuk","year":"2006","journal-title":"Gastroenterology"},{"issue":"01","key":"ref11","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1111\/j.1749-6632.2009.05239.x","article-title":"Role of the polycytin-primary cilia complex in bone development and mechanosensing","volume":"1192","author":"Z S Xiao","year":"2010","journal-title":"Ann N Y Acad Sci"},{"issue":"02","key":"ref12","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1038\/ng1076","article-title":"Polycystins 1 and 2 mediate mechanosensation in the primary cilium of kidney cells","volume":"33","author":"S M Nauli","year":"2003","journal-title":"Nat Genet"},{"issue":"48","key":"ref13","doi-asserted-by":"crossref","first-page":"19138","DOI":"10.1073\/pnas.0705964104","article-title":"Cholangiocyte cilia express TRPV4 and detect changes in luminal tonicity inducing bicarbonate secretion","volume":"104","author":"S A Gradilone","year":"2007","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"04","key":"ref14","doi-asserted-by":"crossref","first-page":"1582","DOI":"10.1002\/hep.30308","article-title":"The chemosensory function of primary cilia regulates cholangiocyte migration, invasion and tumor growth","volume":"69","author":"A P Mansini","year":"2019","journal-title":"Hepatology"},{"issue":"04","key":"ref15","doi-asserted-by":"crossref","first-page":"G725","DOI":"10.1152\/ajpgi.90265.2008","article-title":"Cholangiocyte primary cilia are chemosensory organelles that detect biliary nucleotides via P2Y12 purinergic receptors","volume":"295","author":"A I Masyuk","year":"2008","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"issue":"09","key":"ref16","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.15252\/embr.201540530","article-title":"Ins and outs of GPCR signaling in primary cilia","volume":"16","author":"K B Schou","year":"2015","journal-title":"EMBO Rep"},{"issue":"07","key":"ref17","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1515\/bc.2010.077","article-title":"The membrane-bound bile acid receptor TGR5 (Gpbar-1) is localized in the primary cilium of cholangiocytes","volume":"391","author":"V Keitel","year":"2010","journal-title":"Biol Chem"},{"issue":"03","key":"ref18","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1136\/gutjnl-2015-309458","article-title":"TGR5 is essential for bile acid-dependent cholangiocyte proliferation in vivo and in vitro","volume":"65","author":"M Reich","year":"2016","journal-title":"Gut"},{"issue":"11","key":"ref19","doi-asserted-by":"crossref","first-page":"G1013","DOI":"10.1152\/ajpgi.00383.2012","article-title":"Ciliary subcellular localization of TGR5 determines the cholangiocyte functional response to bile acid signaling","volume":"304","author":"A I Masyuk","year":"2013","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"issue":"02","key":"ref20","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1681\/ASN.2008060564","article-title":"Characterization of PKD protein-positive exosome-like vesicles","volume":"20","author":"M C Hogan","year":"2009","journal-title":"J Am Soc Nephrol"},{"issue":"05","key":"ref21","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1016\/j.tcb.2014.12.008","article-title":"Ciliary ectosomes: transmissions from the cell's antenna","volume":"25","author":"C R Wood","year":"2015","journal-title":"Trends Cell Biol"},{"issue":"04","key":"ref22","doi-asserted-by":"crossref","first-page":"G990","DOI":"10.1152\/ajpgi.00093.2010","article-title":"Biliary exosomes influence cholangiocyte regulatory mechanisms and proliferation through interaction with primary cilia","volume":"299","author":"A I Masyuk","year":"2010","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"issue":"03","key":"ref23","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1097\/MOG.0b013e32834550b4","article-title":"Hedgehog signaling in cholangiocytes","volume":"27","author":"A Omenetti","year":"2011","journal-title":"Curr Opin Gastroenterol"},{"issue":"05","key":"ref24","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1101\/cshperspect.a028175","article-title":"Primary cilia and mammalian Hedgehog signaling","volume":"9","author":"F Bangs","year":"2017","journal-title":"Cold Spring Harb Perspect Biol"},{"issue":"03","key":"ref25","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1016\/j.jhep.2013.11.005","article-title":"Non-canonical Hedgehog signaling contributes to chemotaxis in cholangiocarcinoma","volume":"60","author":"N Razumilava","year":"2014","journal-title":"J Hepatol"},{"issue":"10","key":"ref26","doi-asserted-by":"crossref","first-page":"2251","DOI":"10.1016\/j.ajpath.2018.06.014","article-title":"Blockade of Hedgehog signaling attenuates biliary cystogenesis in the polycystic kidney (PCK) rat","volume":"188","author":"Y Sato","year":"2018","journal-title":"Am J Pathol"},{"issue":"19","key":"ref27","doi-asserted-by":"crossref","first-page":"4774","DOI":"10.3390\/cancers13194774","article-title":"The role of the Hedgehog pathway in cholangiocarcinoma","volume":"13","author":"G Anichini","year":"2021","journal-title":"Cancers (Basel)"},{"issue":"32","key":"ref28","doi-asserted-by":"crossref","first-page":"6850","DOI":"10.1523\/JNEUROSCI.3005-20.2021","article-title":"Multifaceted functions of Rab23 on primary cilium-mediated and Hedgehog signaling-mediated cerebellar granule cell proliferation","volume":"41","author":"C HH Hor","year":"2021","journal-title":"J Neurosci"},{"issue":"01","key":"ref29","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1038\/s41392-021-00762-6","article-title":"Wnt\/\u03b2-catenin signalling: function, biological mechanisms, and therapeutic opportunities","volume":"7","author":"J Liu","year":"2022","journal-title":"Signal Transduct Target Ther"},{"issue":"S 01","key":"ref30","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1111\/liv.14094","article-title":"Experimental models to unravel the molecular pathogenesis, cell of origin and stem cell properties of cholangiocarcinoma","volume":"39","author":"S Vicent","year":"2019","journal-title":"Liver Int"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1101\/gad.349596.122","article-title":"Primary cilia control translation and the cell cycle in medulloblastoma","volume":"36","author":"Y H Youn","year":"2022","journal-title":"Genes Dev"},{"issue":"01","key":"ref32","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1038\/s41392-022-00934-y","article-title":"Notch signaling pathway: architecture, disease, and therapeutics","volume":"7","author":"B Zhou","year":"2022","journal-title":"Signal Transduct Target Ther"},{"issue":"08","key":"ref33","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1111\/pin.13130","article-title":"Notch-Hes1 signaling activation in Caroli disease and polycystic liver disease","volume":"71","author":"K Takahashi","year":"2021","journal-title":"Pathol Int"},{"issue":"03","key":"ref34","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1038\/labinvest.2015.149","article-title":"Inhibition of notch signaling pathway prevents cholestatic liver fibrosis by decreasing the differentiation of hepatic progenitor cells into cholangiocytes","volume":"96","author":"X Zhang","year":"2016","journal-title":"Lab Invest"},{"issue":"09","key":"ref35","doi-asserted-by":"crossref","first-page":"957","DOI":"10.4251\/wjgo.v12.i9.957","article-title":"Notch signalling pathway in development of cholangiocarcinoma","volume":"12","author":"B Rauff","year":"2020","journal-title":"World J Gastrointest Oncol"},{"issue":"09","key":"ref36","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1016\/j.tcb.2015.05.002","article-title":"YAP and TAZ: a nexus for Hippo signaling and beyond","volume":"25","author":"C G Hansen","year":"2015","journal-title":"Trends Cell Biol"},{"issue":"26","key":"ref37","doi-asserted-by":"crossref","first-page":"5528","DOI":"10.1093\/hmg\/dds408","article-title":"The ciliopathy disease protein NPHP9 promotes nuclear delivery and activation of the oncogenic transcriptional regulator TAZ","volume":"21","author":"S Habbig","year":"2012","journal-title":"Hum Mol Genet"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"5370","DOI":"10.1038\/ncomms6370","article-title":"The MST1\/2\u2013SAV1 complex of the Hippo pathway promotes ciliogenesis","volume":"5","author":"M Kim","year":"2014","journal-title":"Nat Commun"},{"issue":"46","key":"ref39","doi-asserted-by":"crossref","first-page":"29001","DOI":"10.1073\/pnas.2009334117","article-title":"TAZ\/Wnt-\u03b2-catenin\/c-MYC axis regulates cystogenesis in polycystic kidney disease","volume":"117","author":"E J Lee","year":"2020","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"01","key":"ref40","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1186\/s13046-022-02394-2","article-title":"The Hippo pathway effector TAZ induces intrahepatic cholangiocarcinoma in mice and is ubiquitously activated in the human disease","volume":"41","author":"A Cigliano","year":"2022","journal-title":"J Exp Clin Cancer Res"},{"issue":"11","key":"ref41","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.1038\/ncb2117","article-title":"Primary cilia regulate mTORC1 activity and cell size through Lkb1","volume":"12","author":"C Boehlke","year":"2010","journal-title":"Nat Cell Biol"},{"issue":"06","key":"ref42","first-page":"11","article-title":"Reciprocal regulation between primary cilia and mTORC1","volume":"11","author":"Y Lai","year":"2020","journal-title":"Genes (Basel)"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.coph.2017.09.008","article-title":"Modulating bile acid pathways and TGR5 receptors for treating liver and GI diseases","volume":"37","author":"H Malhi","year":"2017","journal-title":"Curr Opin Pharmacol"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.1016\/j.bbadis.2017.08.021","article-title":"Bile acid receptors in the biliary tree: TGR5 in physiology and disease","volume":"1864","author":"K Deutschmann","year":"2018","journal-title":"Biochim Biophys Acta Mol Basis Dis"},{"issue":"06","key":"ref45","doi-asserted-by":"crossref","first-page":"1263","DOI":"10.1016\/j.jhep.2010.12.004","article-title":"The bile acid membrane receptor TGR5 as an emerging target in metabolism and inflammation","volume":"54","author":"T WH Pols","year":"2011","journal-title":"J Hepatol"},{"issue":"04","key":"ref46","doi-asserted-by":"crossref","first-page":"1132","DOI":"10.1097\/HEP.0000000000001055","article-title":"Cholangiocyte ciliary defects induce sustained epidermal growth factor receptor signaling","volume":"81","author":"K Pant","year":"2025","journal-title":"Hepatology"},{"issue":"03","key":"ref47","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1016\/j.jhep.2021.03.029","article-title":"Downregulation of TGR5 (GPBAR1) in biliary epithelial cells contributes to the pathogenesis of sclerosing cholangitis","volume":"75","author":"M Reich","year":"2021","journal-title":"J Hepatol"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.1016\/j.bbadis.2017.08.021","article-title":"Bile acid receptors in the biliary tree: TGR5 in physiology and disease","volume":"1864","author":"K Deutschmann","year":"2018","journal-title":"Biochim Biophys Acta Mol Basis Dis"},{"issue":"03","key":"ref49","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1002\/hep.23032","article-title":"The membrane-bound bile acid receptor TGR5 is localized in the epithelium of human gallbladders","volume":"50","author":"V Keitel","year":"2009","journal-title":"Hepatology"},{"issue":"04","key":"ref50","doi-asserted-by":"crossref","first-page":"1197","DOI":"10.1002\/hep.29284","article-title":"TGR5 contributes to hepatic cystogenesis in rodents with polycystic liver diseases through cyclic adenosine monophosphate\/G\u03b1s signaling","volume":"66","author":"T V Masyuk","year":"2017","journal-title":"Hepatology"},{"issue":"20","key":"ref51","doi-asserted-by":"crossref","first-page":"1861","DOI":"10.1016\/j.cub.2005.09.012","article-title":"PDGFRalphaalpha signaling is regulated through the primary cilium in fibroblasts","volume":"15","author":"L Schneider","year":"2005","journal-title":"Curr Biol"},{"issue":"01","key":"ref52","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1002\/jcb.30345","article-title":"PDGF-AA activates AKT and ERK signaling for testicular interstitial Leydig cell growth via primary cilia","volume":"124","author":"Y C Tsai","year":"2023","journal-title":"J Cell Biochem"},{"issue":"06","key":"ref53","doi-asserted-by":"crossref","first-page":"1806","DOI":"10.1016\/j.celrep.2013.05.020","article-title":"TGF-\u03b2 signaling is associated with endocytosis at the pocket region of the primary cilium","volume":"3","author":"C A Clement","year":"2013","journal-title":"Cell Rep"},{"issue":"713","key":"ref54","doi-asserted-by":"crossref","first-page":"eabq5930","DOI":"10.1126\/scitranslmed.abq5930","article-title":"A TGF\u03b2-ECM-integrin signaling axis drives structural reconfiguration of the bile duct to promote polycystic liver disease","volume":"15","author":"S H Waddell","year":"2023","journal-title":"Sci Transl Med"},{"issue":"06","key":"ref55","doi-asserted-by":"crossref","first-page":"2462","DOI":"10.1002\/hep.29708","article-title":"Polycystic liver disease: the interplay of genes causative for hepatic and renal cystogenesis","volume":"67","author":"T V Masyuk","year":"2018","journal-title":"Hepatology"},{"key":"ref56","doi-asserted-by":"crossref","first-page":"166348","DOI":"10.1016\/j.bbadis.2022.166348","article-title":"The genetic of autosomal recessive polycystic kidney disease (ARRPKD)","volume":"1868","author":"P Goggolidou","year":"2022","journal-title":"BBA - Molecular Basis of Disease"},{"issue":"01","key":"ref57","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1681\/ASN.2017050483","article-title":"Genetic complexity of autosomal dominant polycystic kidney and liver diseases","volume":"29","author":"E Cornec-Le Gall","year":"2018","journal-title":"J Am Soc Nephrol"},{"key":"ref58","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1146\/annurev-pathol-042320-121247","article-title":"Polycystic liver disease: advances in understanding and treatment","volume":"17","author":"T V Masyuk","year":"2022","journal-title":"Annu Rev Pathol"},{"issue":"08","key":"ref59","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1038\/s41575-019-0156-4","article-title":"Pathobiology of inherited biliary diseases: a roadmap to understand acquired liver diseases","volume":"16","author":"L Fabris","year":"2019","journal-title":"Nat Rev Gastroenterol Hepatol"},{"issue":"01","key":"ref60","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1053\/j.gastro.2010.04.010","article-title":"Activation of Trpv4 reduces the hyperproliferative phenotype of cystic cholangiocytes from an animal model of ARPKD","volume":"139","author":"S A Gradilone","year":"2010","journal-title":"Gastroenterology"},{"issue":"08","key":"ref61","doi-asserted-by":"crossref","first-page":"950","DOI":"10.2174\/1389450116666150427161743","article-title":"Therapeutic targets in polycystic liver disease","volume":"18","author":"T V Masyuk","year":"2017","journal-title":"Curr Drug Targets"},{"issue":"02","key":"ref62","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.krcp.2014.05.002","article-title":"Cyst growth, polycystins, and primary cilia in autosomal dominant polycystic kidney disease","volume":"33","author":"S H Lee","year":"2014","journal-title":"Kidney Res Clin Pract"},{"issue":"07","key":"ref63","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1038\/s41581-019-0143-6","article-title":"Structure and function of polycystins: insights into polycystic kidney disease","volume":"15","author":"D Douguet","year":"2019","journal-title":"Nat Rev Nephrol"},{"key":"ref64","first-page":"a028209","article-title":"Ciliary mechanisms of cyst formation in polycystic kidney disease","volume":"9","author":"M Ma","year":"2017","journal-title":"Csh Perspect Biol"},{"issue":"04","key":"ref65","doi-asserted-by":"crossref","first-page":"1274","DOI":"10.1097\/HEP.0000000000000029","article-title":"Liver-restricted deletion of the biliary atresia candidate gene Pkd1l1 causes bile duct dysmorphogenesis and ciliopathy","volume":"77","author":"D J Hellen","year":"2023","journal-title":"Hepatology"},{"issue":"01","key":"ref66","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1097\/MPG.0b013e318296e525","article-title":"Extrahepatic cholangiocyte cilia are abnormal in biliary atresia","volume":"57","author":"S Karjoo","year":"2013","journal-title":"J Pediatr Gastroenterol Nutr"},{"issue":"04","key":"ref67","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1097\/MPG.0b013e318200eb6f","article-title":"Investigation of primary cilia in the pathogenesis of biliary atresia","volume":"52","author":"J L Hartley","year":"2011","journal-title":"J Pediatr Gastroenterol Nutr"},{"key":"ref68","doi-asserted-by":"crossref","first-page":"103530","DOI":"10.1016\/j.ebiom.2021.103530","article-title":"Identification of a wide spectrum of ciliary gene mutations in nonsyndromic biliary atresia patients implicates ciliary dysfunction as a novel disease mechanism","volume":"71","author":"W Y Lam","year":"2021","journal-title":"EBioMedicine"},{"issue":"06","key":"ref69","doi-asserted-by":"crossref","first-page":"1385","DOI":"10.1016\/j.jhep.2023.07.039","article-title":"Biliary atresia is associated with polygenic susceptibility in ciliogenesis and planar polarity effector genes","volume":"79","author":"J T Glessner","year":"2023","journal-title":"J Hepatol"},{"issue":"07","key":"ref70","doi-asserted-by":"crossref","first-page":"2259","DOI":"10.1158\/0008-5472.CAN-12-2938","article-title":"HDAC6 inhibition restores ciliary expression and decreases tumor growth","volume":"73","author":"S A Gradilone","year":"2013","journal-title":"Cancer Res"},{"issue":"04","key":"ref71","doi-asserted-by":"crossref","first-page":"166335","DOI":"10.1016\/j.bbadis.2021.166335","article-title":"Deletion of kif3a in CK19 positive cells leads to primary cilia loss, biliary cell proliferation and cystic liver lesions in TAA-treated mice","volume":"1868","author":"J Chen","year":"2022","journal-title":"Biochim Biophys Acta Mol Basis Dis"},{"issue":"06","key":"ref72","doi-asserted-by":"crossref","first-page":"3235","DOI":"10.1002\/hep.32080","article-title":"Histone deacetylase sirtuin 1 promotes loss of primary cilia in cholangiocarcinoma","volume":"74","author":"K Pant","year":"2021","journal-title":"Hepatology"},{"key":"ref73","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1002\/hep.29832","article-title":"MiR-433 and miR-22 dysregulations induce HDAC6 overexpression and ciliary loss in cholangiocarcinoma","volume":"68","author":"A P Mansini","year":"2018","journal-title":"Hepatology"},{"key":"ref74","doi-asserted-by":"crossref","first-page":"809382","DOI":"10.3389\/fcell.2021.809382","article-title":"Short-chain fatty acid butyrate induces cilia formation and potentiates the effects of HDAC6 inhibitors in cholangiocarcinoma cells","volume":"9","author":"K Pant","year":"2022","journal-title":"Front Cell Dev Biol"},{"issue":"03","key":"ref75","doi-asserted-by":"crossref","first-page":"9","DOI":"10.3390\/cells9030780","article-title":"Role of histone deacetylases in carcinogenesis: potential role in cholangiocarcinoma","volume":"9","author":"K Pant","year":"2020","journal-title":"Cells"},{"issue":"05","key":"ref76","doi-asserted-by":"crossref","first-page":"12","DOI":"10.3390\/cells12050775","article-title":"The NAMPT inhibitor FK866 in combination with cisplatin reduces cholangiocarcinoma cells growth","volume":"12","author":"K Pant","year":"2023","journal-title":"Cells"},{"issue":"08","key":"ref77","doi-asserted-by":"crossref","first-page":"1528","DOI":"10.1016\/j.ajpath.2024.04.010","article-title":"NAMPT overexpression drives cell growth in polycystic liver disease through mitochondrial metabolism regulation","volume":"194","author":"K Pant","year":"2024","journal-title":"Am J Pathol"},{"key":"ref78","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1016\/j.redox.2017.03.006","article-title":"Butyrate induces ROS-mediated apoptosis by modulating miR-22\/SIRT-1 pathway in hepatic cancer cells","volume":"12","author":"K Pant","year":"2017","journal-title":"Redox Biol"},{"issue":"06","key":"ref79","doi-asserted-by":"crossref","first-page":"G1022","DOI":"10.1152\/ajpgi.00033.2020","article-title":"HDAC6-dependent ciliophagy is involved in ciliary loss and cholangiocarcinoma growth in human cells and murine models","volume":"318","author":"E Peixoto","year":"2020","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"issue":"04","key":"ref80","doi-asserted-by":"crossref","first-page":"e105120","DOI":"10.15252\/embj.2020105120","article-title":"Regulation of autophagosome biogenesis by OFD1-mediated selective autophagy","volume":"40","author":"M Morleo","year":"2021","journal-title":"EMBO J"},{"issue":"03","key":"ref81","doi-asserted-by":"crossref","first-page":"207","DOI":"10.31662\/jmaj.2021-0090","article-title":"Autophagy and ciliogenesis","volume":"4","author":"Y Yamamoto","year":"2021","journal-title":"JMA J"},{"issue":"07","key":"ref82","first-page":"13","article-title":"HDAC6 signaling at primary cilia promotes proliferation and restricts differentiation of glioma cells","volume":"13","author":"P Shi","year":"2021","journal-title":"Cancers (Basel)"},{"key":"ref83","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.jhep.2017.03.022","article-title":"Electronic address eee, European Association for the study of the L: EASL clinical practice guidelines: the diagnosis and management of patients with primary biliary cholangitis","volume":"67","author":"European Association for the Study of the Liver","year":"2017","journal-title":"J Hepatol"},{"issue":"05","key":"ref84","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1038\/nrgastro.2016.154","article-title":"Genetics of primary sclerosing cholangitis and pathophysiological implications","volume":"14","author":"X Jiang","year":"2017","journal-title":"Nat Rev Gastroenterol Hepatol"},{"issue":"01","key":"ref85","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1007\/s12016-019-08764-7","article-title":"Cholangiocarcinoma in patients with primary sclerosing cholangitis (PSC): a comprehensive review","volume":"58","author":"J Song","year":"2020","journal-title":"Clin Rev Allergy Immunol"},{"issue":"08","key":"ref86","doi-asserted-by":"crossref","first-page":"2065","DOI":"10.1016\/j.cgh.2023.04.004","article-title":"Recent advances in the management of primary sclerosing cholangitis","volume":"21","author":"D N Assis","year":"2023","journal-title":"Clin Gastroenterol Hepatol"},{"issue":"03","key":"ref87","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1159\/000371696","article-title":"TGR5 in the cholangiociliopathies","volume":"33","author":"T V Masyuk","year":"2015","journal-title":"Dig Dis"},{"issue":"02","key":"ref88","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1002\/hep.30210","article-title":"Neoplastic transformation of the peribiliary stem cell niche in cholangiocarcinoma arisen in primary sclerosing cholangitis","volume":"69","author":"G Carpino","year":"2019","journal-title":"Hepatology"},{"key":"ref89","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/S0168-8278(15)30170-7","article-title":"Mutations in Dcdc2, encoding doublecortin domain-containing protein 2, cause neonatal sclerosing cholangitis","volume":"62","author":"T Grammatikopoulos","year":"2015","journal-title":"J Hepatol"},{"issue":"12","key":"ref90","doi-asserted-by":"crossref","first-page":"2230","DOI":"10.1111\/liv.14180","article-title":"Pathogenesis, diagnosis and treatment of premalignant and malignant stages of cholangiocarcinoma in primary sclerosing cholangitis","volume":"39","author":"M M Grimsrud","year":"2019","journal-title":"Liver Int"},{"issue":"01","key":"ref91","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1002\/j.2040-4603.2013.tb00495.x","article-title":"Physiology of cholangiocytes","volume":"3","author":"J H Tabibian","year":"2013","journal-title":"Compr Physiol"},{"key":"ref92","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1177\/15330338221097203","article-title":"Hepatobiliary cancers: progress in diagnosis, pathogenesis, and treatment","volume":"21","author":"K Pant","year":"2022","journal-title":"Technol Cancer Res Treat"},{"issue":"05","key":"ref93","doi-asserted-by":"crossref","first-page":"1110","DOI":"10.1002\/hep.32298","article-title":"Autophagy promotes hepatic cystogenesis in polycystic liver disease by depletion of cholangiocyte ciliogenic proteins","volume":"75","author":"A I Masyuk","year":"2022","journal-title":"Hepatology"},{"issue":"06","key":"ref94","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1016\/j.jhep.2024.06.002","article-title":"Primary cilia as a targetable node between biliary injury, senescence and regeneration in liver transplantation","volume":"81","author":"H Esser","year":"2024","journal-title":"J Hepatol"},{"issue":"03","key":"ref95","doi-asserted-by":"crossref","first-page":"1269","DOI":"10.1172\/JCI76452","article-title":"WNT signaling drives cholangiocarcinoma growth and can be pharmacologically inhibited","volume":"125","author":"L Boulter","year":"2015","journal-title":"J Clin Invest"},{"issue":"09","key":"ref97","doi-asserted-by":"crossref","first-page":"1677","DOI":"10.1136\/gutjnl-2019-319091","article-title":"TGF-\u03b22 silencing to target biliary-derived liver diseases","volume":"69","author":"A Dropmann","year":"2020","journal-title":"Gut"},{"issue":"01","key":"ref98","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1038\/modpathol.2011.133","article-title":"The expression of phospho-AKT1 and phospho-MTOR is associated with a favorable prognosis independent of PTEN expression in intrahepatic cholangiocarcinomas","volume":"25","author":"D Lee","year":"2012","journal-title":"Mod Pathol"},{"issue":"03","key":"ref99","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1016\/j.jhep.2016.10.032","article-title":"Adenylyl cyclase 5 links changes in calcium homeostasis to cAMP-dependent cyst growth in polycystic liver disease","volume":"66","author":"C Spirli","year":"2017","journal-title":"J Hepatol"}],"container-title":["Seminars in Liver Disease"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/a-2563-9791.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,10]],"date-time":"2025-09-10T22:47:32Z","timestamp":1757544452000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/a-2563-9791"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,21]]},"references-count":98,"journal-issue":{"issue":"03","published-online":{"date-parts":[[2025,9,10]]},"published-print":{"date-parts":[[2025,9]]}},"URL":"https:\/\/doi.org\/10.1055\/a-2563-9791","archive":["Portico","CLOCKSS"],"relation":{},"ISSN":["0272-8087","1098-8971"],"issn-type":[{"value":"0272-8087","type":"print"},{"value":"1098-8971","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,3,21]]},"published":{"date-parts":[[2025,3,21]]}}}