{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T12:00:08Z","timestamp":1789992008523,"version":"4.0.1"},"reference-count":45,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T00:00:00Z","timestamp":1780963200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T00:00:00Z","timestamp":1789948800000},"content-version":"vor","delay-in-days":104,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Commun Biol"],"DOI":"10.1038\/s42003-026-10476-6","type":"journal-article","created":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T15:15:20Z","timestamp":1781018120000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["P-STAT3-dependent SPP1 transcription in cholangiocytes drives hepatic stellate cells activation in congenital hepatic fibrosis"],"prefix":"10.1038","volume":"9","author":[{"given":"Mengfan","family":"Jiao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ye","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xizhi","family":"Yin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoxue","family":"Hou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zixing","family":"Dai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingling","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6557-1654","authenticated-orcid":false,"given":"Chuanlong","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,9]]},"reference":[{"key":"10476_CR1","first-page":"984","volume":"66","author":"A Parkash","year":"2016","unstructured":"Parkash, A., Cheema, H. A., Malik, H. S. & Fayyaz, Z. Congenital hepatic fibrosis: clinical presentation, laboratory features and management at a tertiary care hospital of Lahore. J. Pak. Med. Assoc. 66, 984\u2013988 (2016).","journal-title":"J. Pak. Med. Assoc."},{"key":"10476_CR2","doi-asserted-by":"publisher","first-page":"340","DOI":"10.1053\/j.gastro.2022.09.019","volume":"164","author":"R Liu","year":"2023","unstructured":"Liu, R., Dai, Z. & Zhu, C. A rare cause of liver fibrosis in an adolescent woman. Gastroenterology 164, 340\u2013343 (2023).","journal-title":"Gastroenterology"},{"key":"10476_CR3","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1590\/S0101-28002010000300007","volume":"32","author":"NF Dias","year":"2010","unstructured":"Dias, N. F., Lanzarini, V., Onuchic, L. F. & Koch, V. H. Clinical aspects of autosomal recessive polycystic kidney disease. J. Bras. Nefrol. 32, 263\u2013267 (2010).","journal-title":"J. Bras. Nefrol."},{"key":"10476_CR4","doi-asserted-by":"publisher","first-page":"360","DOI":"10.1034\/j.1600-6143.2002.20412.x","volume":"2","author":"K Khan","year":"2002","unstructured":"Khan, K., Schwarzenberg, S. J., Sharp, H. L., Matas, A. J. & Chavers, B. M. Morbidity from congenital hepatic fibrosis after renal transplantation for autosomal recessive polycystic kidney disease. Am. J. Transplant. 2, 360\u2013365 (2002).","journal-title":"Am. J. Transplant."},{"key":"10476_CR5","doi-asserted-by":"publisher","first-page":"1281","DOI":"10.1111\/tri.13884","volume":"34","author":"WK Wu","year":"2021","unstructured":"Wu, W. K. et al. Liver transplantation for congenital hepatic fibrosis. Transpl. Int. 34, 1281\u20131292 (2021).","journal-title":"Transpl. Int."},{"key":"10476_CR6","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/4918798","volume":"2016","author":"L Jiang","year":"2016","unstructured":"Jiang, L., Fang, P., Weemhoff, J. L., Apte, U. & Pritchard, M. T. Evidence for a \u201cpathogenic triumvirate\u201d in congenital hepatic fibrosis in autosomal recessive polycystic kidney disease. Biomed. Res. Int. 2016, 4918798 (2016).","journal-title":"Biomed. Res. Int."},{"key":"10476_CR7","doi-asserted-by":"publisher","first-page":"221","DOI":"10.3389\/fped.2017.00221","volume":"5","author":"C Bergmann","year":"2017","unstructured":"Bergmann, C. Genetics of autosomal recessive polycystic kidney disease and its differential diagnoses. Front. Pediatr. 5, 221 (2017).","journal-title":"Front. Pediatr."},{"key":"10476_CR8","doi-asserted-by":"publisher","first-page":"2246","DOI":"10.1097\/01.ASN.0000030392.19694.9D","volume":"13","author":"Y Nagasawa","year":"2002","unstructured":"Nagasawa, Y. et al. Identification and characterization of Pkhd1, the mouse orthologue of the human ARPKD gene. J. Am. Soc. Nephrol. 13, 2246\u20132258 (2002).","journal-title":"J. Am. Soc. Nephrol."},{"key":"10476_CR9","doi-asserted-by":"publisher","first-page":"1374","DOI":"10.1681\/ASN.2007010125","volume":"18","author":"S Rossetti","year":"2007","unstructured":"Rossetti, S. & Harris, P. C. Genotype-phenotype correlations in autosomal dominant and autosomal recessive polycystic kidney disease. J. Am. Soc. Nephrol. 18, 1374\u20131380 (2007).","journal-title":"J. Am. Soc. Nephrol."},{"key":"10476_CR10","doi-asserted-by":"publisher","first-page":"1305","DOI":"10.1086\/340448","volume":"70","author":"LF Onuchic","year":"2002","unstructured":"Onuchic, L. F. et al. PKHD1, the polycystic kidney and hepatic disease 1 gene, encodes a novel large protein containing multiple immunoglobulin-like plexin-transcription-factor domains and parallel beta-helix 1 repeats. Am. J. Hum. Genet. 70, 1305\u20131317 (2002).","journal-title":"Am. J. Hum. Genet."},{"key":"10476_CR11","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1055\/s-2007-1007159","volume":"18","author":"C Colombo","year":"1998","unstructured":"Colombo, C., Battezzati, P. M., Strazzabosco, M. & Podda, M. Liver and biliary problems in cystic fibrosis. Semin. Liver Dis. 18, 227\u2013235 (1998).","journal-title":"Semin. Liver Dis."},{"key":"10476_CR12","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1016\/j.ebiom.2019.01.009","volume":"40","author":"J Li","year":"2019","unstructured":"Li, J. et al. Autocrine CTHRC1 activates hepatic stellate cells and promotes liver fibrosis by activating TGF-\u03b2 signaling. EBioMedicine 40, 43\u201355 (2019).","journal-title":"EBioMedicine"},{"key":"10476_CR13","doi-asserted-by":"publisher","first-page":"1403","DOI":"10.1007\/s10753-024-01984-w","volume":"47","author":"C Wang","year":"2024","unstructured":"Wang, C. et al. Phillygenin inhibits TGF-\u03b21-induced hepatic stellate cell activation and inflammation: regulation of the Bax\/Bcl-2 and Wnt\/\u03b2-catenin pathways. Inflammation 47, 1403\u20131422 (2024).","journal-title":"Inflammation"},{"key":"10476_CR14","doi-asserted-by":"publisher","first-page":"965","DOI":"10.1002\/hep.28382","volume":"63","author":"L Locatelli","year":"2016","unstructured":"Locatelli, L. et al. Macrophage recruitment by fibrocystin-defective biliary epithelial cells promotes portal fibrosis in congenital hepatic fibrosis. Hepatology 63, 965\u2013982 (2016).","journal-title":"Hepatology"},{"key":"10476_CR15","doi-asserted-by":"publisher","first-page":"1317","DOI":"10.1002\/hep.30662","volume":"70","author":"R Liu","year":"2019","unstructured":"Liu, R. et al. Cholangiocyte-derived exosomal long noncoding RNA H19 promotes hepatic stellate cell activation and cholestatic liver fibrosis. Hepatology 70, 1317\u20131335 (2019).","journal-title":"Hepatology"},{"key":"10476_CR16","doi-asserted-by":"publisher","first-page":"1940","DOI":"10.1093\/hmg\/ddm141","volume":"16","author":"MA Garcia-Gonzalez","year":"2007","unstructured":"Garcia-Gonzalez, M. A. et al. Genetic interaction studies link autosomal dominant and recessive polycystic kidney disease in a common pathway. Hum. Mol. Genet. 16, 1940\u20131950 (2007).","journal-title":"Hum. Mol. Genet."},{"key":"10476_CR17","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1186\/s12866-025-03892-x","volume":"25","author":"M Jiao","year":"2025","unstructured":"Jiao, M. et al. Multi-omics analysis of host-microbiome interactions in a mouse model of congenital hepatic fibrosis. BMC Microbiol. 25, 176 (2025).","journal-title":"BMC Microbiol."},{"key":"10476_CR18","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2022.907901","volume":"13","author":"W Chen","year":"2022","unstructured":"Chen, W. et al. Highly efficient methods to culture mouse cholangiocytes and small intestine organoids. Front. Microbiol. 13, 907901 (2022).","journal-title":"Front. Microbiol."},{"key":"10476_CR19","doi-asserted-by":"crossref","unstructured":"Cordido, A., Vizoso-Gonzalez, M. & Garcia-Gonzalez, M. A. Molecular pathophysiology of autosomal recessive polycystic kidney disease. Int. J. Mol. Sci. 22, 6523 (2021).","DOI":"10.3390\/ijms22126523"},{"key":"10476_CR20","doi-asserted-by":"publisher","first-page":"418","DOI":"10.1016\/j.matbio.2005.05.005","volume":"24","author":"Y Yokosaki","year":"2005","unstructured":"Yokosaki, Y., Tanaka, K., Higashikawa, F., Yamashita, K. & Eboshida, A. Distinct structural requirements for binding of the integrins alphavbeta6, alphavbeta3, alphavbeta5, alpha5beta1 and alpha9beta1 to osteopontin. Matrix Biol. 24, 418\u2013427 (2005).","journal-title":"Matrix Biol."},{"key":"10476_CR21","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1186\/s11658-018-0078-0","volume":"23","author":"M Galoczova","year":"2018","unstructured":"Galoczova, M., Coates, P. & Vojtesek, B. STAT3, stem cells, cancer stem cells and p63. Cell. Mol. Biol. Lett. 23, 12 (2018).","journal-title":"Cell. Mol. Biol. Lett."},{"key":"10476_CR22","doi-asserted-by":"publisher","first-page":"R125","DOI":"10.1093\/hmg\/ddq365","volume":"19","author":"DG MacArthur","year":"2010","unstructured":"MacArthur, D. G. & Tyler-Smith, C. Loss-of-function variants in the genomes of healthy humans. Hum. Mol. Genet. 19, R125\u2013R130 (2010).","journal-title":"Hum. Mol. Genet."},{"key":"10476_CR23","doi-asserted-by":"publisher","first-page":"611","DOI":"10.1016\/j.jpeds.2014.06.015","volume":"165","author":"LM Guay-Woodford","year":"2014","unstructured":"Guay-Woodford, L. M. et al. Consensus expert recommendations for the diagnosis and management of autosomal recessive polycystic kidney disease: report of an international conference. J. Pediatr. 165, 611\u2013617 (2014).","journal-title":"J. Pediatr."},{"key":"10476_CR24","doi-asserted-by":"publisher","first-page":"160","DOI":"10.1016\/j.ymgme.2009.10.010","volume":"99","author":"M Gunay-Aygun","year":"2010","unstructured":"Gunay-Aygun, M. et al. PKHD1 sequence variations in 78 children and adults with autosomal recessive polycystic kidney disease and congenital hepatic fibrosis. Mol. Genet. Metab. 99, 160\u2013173 (2010).","journal-title":"Mol. Genet. Metab."},{"key":"10476_CR25","doi-asserted-by":"publisher","first-page":"417","DOI":"10.2353\/ajpath.2008.070381","volume":"172","author":"AR Gallagher","year":"2008","unstructured":"Gallagher, A. R. et al. Biliary and pancreatic dysgenesis in mice harboring a mutation in Pkhd1. Am. J. Pathol. 172, 417\u2013429 (2008).","journal-title":"Am. J. Pathol."},{"key":"10476_CR26","doi-asserted-by":"publisher","unstructured":"Cheng, C., Chen, W., Jin, H. & Chen, X. A review of single-cell RNA-Seq annotation, integration, and cell-cell communication. Cells 12, https:\/\/doi.org\/10.3390\/cells12151970 (2023).","DOI":"10.3390\/cells12151970"},{"key":"10476_CR27","doi-asserted-by":"publisher","first-page":"1082","DOI":"10.1038\/labinvest.2013.104","volume":"93","author":"T-M Leung","year":"2013","unstructured":"Leung, T.-M., Wang, X., Kitamura, N., Fiel, M. I. & Nieto, N. Osteopontin delays resolution of liver fibrosis. Lab. Investig. 93, 1082\u20131089 (2013).","journal-title":"Lab. Investig."},{"key":"10476_CR28","doi-asserted-by":"publisher","first-page":"1344","DOI":"10.1002\/hep4.1237","volume":"2","author":"O Glass","year":"2018","unstructured":"Glass, O. et al. Serum interleukin-8, osteopontin, and monocyte chemoattractant protein 1 are associated with hepatic fibrosis in patients with nonalcoholic fatty liver disease. Hepatol. Commun. 2, 1344\u20131355 (2018).","journal-title":"Hepatol. Commun."},{"key":"10476_CR29","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1007\/s12079-020-00554-7","volume":"14","author":"M Honda","year":"2020","unstructured":"Honda, M., Kimura, C., Uede, T. & Kon, S. Neutralizing antibody against osteopontin attenuates non-alcoholic steatohepatitis in mice. J. Cell Commun. Signal. 14, 223\u2013232 (2020).","journal-title":"J. Cell Commun. Signal."},{"key":"10476_CR30","doi-asserted-by":"publisher","unstructured":"Yan, T. et al. Hepatocyte-specific CCAAT\/enhancer binding protein \u03b1 restricts liver fibrosis progression. J. Clin. Investig. 134, https:\/\/doi.org\/10.1172\/jci166731 (2024).","DOI":"10.1172\/jci166731"},{"key":"10476_CR31","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1007\/s00251-022-01276-3","volume":"75","author":"DE Adams","year":"2023","unstructured":"Adams, D. E., Heuer, L. S., Rojas, M., Zhang, W. & Ridgway, W. M. Mutated Pkhd1 alone is sufficient to cause autoimmune biliary disease on the nonobese diabetic (NOD) genetic background. Immunogenetics 75, 27\u201337 (2023).","journal-title":"Immunogenetics"},{"key":"10476_CR32","doi-asserted-by":"publisher","unstructured":"Cannito, S. et al. Fibroinflammatory liver injuries as preneoplastic condition in cholangiopathies. Int. J. Mol. Sci. 19, https:\/\/doi.org\/10.3390\/ijms19123875 (2018).","DOI":"10.3390\/ijms19123875"},{"key":"10476_CR33","doi-asserted-by":"publisher","first-page":"1594","DOI":"10.1002\/hep.31582","volume":"73","author":"Z Song","year":"2021","unstructured":"Song, Z. et al. Osteopontin takes center stage in chronic liver disease. Hepatology 73, 1594\u20131608 (2021).","journal-title":"Hepatology"},{"key":"10476_CR34","doi-asserted-by":"publisher","first-page":"1903","DOI":"10.1002\/hep.29652","volume":"67","author":"E Kaffe","year":"2018","unstructured":"Kaffe, E. et al. \u03b2-Catenin and interleukin-1\u03b2-dependent chemokine (C-X-C motif) ligand 10 production drives progression of disease in a mouse model of congenital hepatic fibrosis. Hepatology 67, 1903\u20131919 (2018).","journal-title":"Hepatology"},{"key":"10476_CR35","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1016\/j.omtn.2023.07.012","volume":"33","author":"S Bala","year":"2023","unstructured":"Bala, S. et al. Therapeutic inhibition of miR-155 attenuates liver fibrosis via STAT3 signaling. Mol. Ther. Nucleic Acids 33, 413\u2013427 (2023).","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"10476_CR36","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1016\/j.jhep.2024.02.032","volume":"81","author":"S He","year":"2024","unstructured":"He, S. et al. Endothelial POFUT1 controls injury-induced liver fibrosis by repressing fibrinogen synthesis. J. Hepatol. 81, 135\u2013148 (2024).","journal-title":"J. Hepatol."},{"key":"10476_CR37","doi-asserted-by":"publisher","unstructured":"Guo, Y. et al. Biliary YB-1\/GLI2 axis facilitates ductular reaction and promotes hepatic stellate cell activation via SPP1\/integrin \u03b1v\u03b21 signaling during liver fibrogenesis. Hepatology, https:\/\/doi.org\/10.1097\/hep.0000000000001458 (2025).","DOI":"10.1097\/hep.0000000000001458"},{"key":"10476_CR38","doi-asserted-by":"publisher","unstructured":"Zhu, C. et al. Hepatocyte notch activation induces liver fibrosis in nonalcoholic steatohepatitis. Sci. Transl. Med. 10, https:\/\/doi.org\/10.1126\/scitranslmed.aat0344 (2018).","DOI":"10.1126\/scitranslmed.aat0344"},{"key":"10476_CR39","doi-asserted-by":"publisher","first-page":"594","DOI":"10.1002\/hep.24701","volume":"55","author":"R Urtasun","year":"2012","unstructured":"Urtasun, R. et al. Osteopontin, an oxidant stress sensitive cytokine, up-regulates collagen-I via integrin \u03b1(V)\u03b2(3) engagement and PI3K\/pAkt\/NF\u03baB signaling. Hepatology 55, 594\u2013608 (2012).","journal-title":"Hepatology"},{"key":"10476_CR40","doi-asserted-by":"publisher","unstructured":"Lee, S., Zhou, P., Whyte, S. & Shin, S. Adeno-associated virus serotype 8-mediated genetic labeling of cholangiocytes in the neonatal murine liver. Pharmaceutics 12, https:\/\/doi.org\/10.3390\/pharmaceutics12040351 (2020).","DOI":"10.3390\/pharmaceutics12040351"},{"key":"10476_CR41","doi-asserted-by":"publisher","first-page":"1282","DOI":"10.1016\/j.ymthe.2025.01.041","volume":"33","author":"CJ Walkey","year":"2025","unstructured":"Walkey, C. J. et al. A comprehensive atlas of AAV tropism in the mouse. Mol. Ther. 33, 1282\u20131299 (2025).","journal-title":"Mol. Ther."},{"key":"10476_CR42","doi-asserted-by":"publisher","first-page":"1829","DOI":"10.1242\/dev.129.8.1829","volume":"129","author":"C Coffinier","year":"2002","unstructured":"Coffinier, C. et al. Bile system morphogenesis defects and liver dysfunction upon targeted deletion of HNF1beta. Development 129, 1829\u20131838 (2002).","journal-title":"Development"},{"key":"10476_CR43","doi-asserted-by":"publisher","first-page":"4233","DOI":"10.1242\/dev.02591","volume":"133","author":"H Yamasaki","year":"2006","unstructured":"Yamasaki, H. et al. Suppression of C\/EBPalpha expression in periportal hepatoblasts may stimulate biliary cell differentiation through increased Hnf6 and Hnf1b expression. Development 133, 4233\u20134243 (2006).","journal-title":"Development"},{"key":"10476_CR44","doi-asserted-by":"publisher","first-page":"1632","DOI":"10.1002\/hep.26131","volume":"57","author":"K Isse","year":"2013","unstructured":"Isse, K. et al. Preexisting epithelial diversity in normal human livers: a tissue-tethered cytometric analysis in portal\/periportal epithelial cells. Hepatology 57, 1632\u20131643 (2013).","journal-title":"Hepatology"},{"key":"10476_CR45","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-26410-9","volume":"12","author":"Y Guan","year":"2021","unstructured":"Guan, Y. et al. A human multi-lineage hepatic organoid model for liver fibrosis. Nat. Commun. 12, 6138 (2021).","journal-title":"Nat. Commun."}],"container-title":["Communications Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s42003-026-10476-6","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s42003-026-10476-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s42003-026-10476-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T11:03:58Z","timestamp":1789988638000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s42003-026-10476-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,9]]},"references-count":45,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["10476"],"URL":"https:\/\/doi.org\/10.1038\/s42003-026-10476-6","relation":{},"ISSN":["2399-3642"],"issn-type":[{"value":"2399-3642","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,9]]},"assertion":[{"value":"23 September 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 June 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 June 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Ethics"}}],"article-number":"1224"}}