{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T18:03:38Z","timestamp":1774029818448,"version":"3.50.1"},"reference-count":41,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T00:00:00Z","timestamp":1770940800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T00:00:00Z","timestamp":1773964800000},"content-version":"vor","delay-in-days":35,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Transl Med"],"DOI":"10.1186\/s12967-026-07727-9","type":"journal-article","created":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T17:05:46Z","timestamp":1771002346000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Metamorphosing macrophages promote placental fibrosis by upregulating the transcription factor STAT5A"],"prefix":"10.1186","volume":"24","author":[{"given":"Aixing","family":"Chen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaomei","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E.","family":"Liao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5312-546X","authenticated-orcid":false,"given":"Yong","family":"Shao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,2,13]]},"reference":[{"issue":"2","key":"7727_CR1","doi-asserted-by":"publisher","first-page":"467","DOI":"10.1002\/hep.20336","volume":"40","author":"A Glantz","year":"2004","unstructured":"Glantz A, Marschall HU, Mattsson LA. Intrahepatic cholestasis of pregnancy: relationships between bile acid levels and fetal complication rates. Hepatology. 2004;40(2):467\u201374.","journal-title":"Hepatology"},{"issue":"1","key":"7727_CR2","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1053\/j.gastro.2022.01.060","volume":"163","author":"NA Terrault","year":"2022","unstructured":"Terrault NA, Williamson C. Pregnancy-associated liver diseases. Gastroenterology. 2022;163(1):97\u2013117.e1.","journal-title":"Gastroenterology"},{"key":"7727_CR3","doi-asserted-by":"publisher","first-page":"849","DOI":"10.1016\/S0140-6736(19)31270-X","volume":"394","author":"LC Chappell","year":"2019","unstructured":"Chappell LC, Bell JL, Smith A, et al. Ursodeoxycholic acid versus placebo in women with intrahepatic cholestasis of pregnancy (PITCHES): a randomised controlled trial. Lancet. 2019;394:849\u201360.","journal-title":"Lancet"},{"issue":"3","key":"7727_CR4","doi-asserted-by":"publisher","first-page":"1040","DOI":"10.1007\/s12072-023-10610-0","volume":"18","author":"S Feng","year":"2024","unstructured":"Feng S, Xie X, Li J, et al. Bile acids induce liver fibrosis through the NLRP3inflammasome pathway and the mechanism of FXR inhibition of NLRP3 activation. Hepatol Int. 2024;18(3):1040\u201352.","journal-title":"Hepatol Int"},{"issue":"2","key":"7727_CR5","doi-asserted-by":"publisher","first-page":"465","DOI":"10.3350\/cmh.2022.0327","volume":"29","author":"J Yang","year":"2023","unstructured":"Yang J, Tang X, Liang Z, et al. Taurocholic acid promotes hepatic stellate cell activation via S1PR2\/p38 MAPK\/YAP signaling under cholestatic conditions. Clin Mol Hepatol. 2023;29(2):465\u201381.","journal-title":"Clin Mol Hepatol"},{"issue":"11","key":"7727_CR6","doi-asserted-by":"publisher","first-page":"914","DOI":"10.1016\/j.placenta.2012.08.005","volume":"33","author":"E Wikstr\u00f6m Shemer","year":"2012","unstructured":"Wikstr\u00f6m Shemer E, Thorsell M, \u00d6stlund E, et al. Stereological assessment of placental morphology in intrahepatic cholestasis of pregnancy. Placenta. 2012;33(11):914\u201318.","journal-title":"Placenta"},{"issue":"1","key":"7727_CR7","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1111\/imr.13080","volume":"308","author":"H True","year":"2022","unstructured":"True H, Blanton M, Sureshchandra S, et al. Monocytes and macrophages in pregnancy: the good, the bad, and the ugly. Immunol Rev. 2022;308(1):77\u201392.","journal-title":"Immunol Rev"},{"key":"7727_CR8","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1016\/j.placenta.2018.04.012","volume":"69","author":"MM Faas","year":"2018","unstructured":"Faas MM, De Vos P. Innate immune cells in the placental bed in healthy pregnancy and preeclampsia. Placenta. 2018;69:125\u201333.","journal-title":"Placenta"},{"issue":"4","key":"7727_CR9","doi-asserted-by":"publisher","first-page":"e2078","DOI":"10.1371\/journal.pone.0002078","volume":"3","author":"C Gustafsson","year":"2008","unstructured":"Gustafsson C, Mj\u00f6sberg J, Matussek A, et al. Gene expression profiling of human decidual macrophages: evidence for immunosuppressive phenotype. PLoS One. 2008;3(4):e2078.","journal-title":"PLoS One"},{"issue":"11","key":"7727_CR10","doi-asserted-by":"publisher","first-page":"5501","DOI":"10.4049\/jimmunol.1300988","volume":"191","author":"A Ben Amara","year":"2013","unstructured":"Ben Amara A, Gorvel L, Baulan K, et al. Placental macrophages are impaired in chorioamnionitis, an infectious pathology of the placenta. J Immunol. 2013;191(11):5501\u201314.","journal-title":"J Immunol"},{"issue":"7","key":"7727_CR11","doi-asserted-by":"publisher","first-page":"3671","DOI":"10.4049\/jimmunol.1100130","volume":"187","author":"J Svensson","year":"2011","unstructured":"Svensson J, Jenmalm MC, Matussek A, et al. Macrophages at the fetal-maternal interface express markers of alternative activation and are induced by M-CSF and IL-10. J Immunol. 2011;187(7):3671\u201382.","journal-title":"J Immunol"},{"key":"7727_CR12","doi-asserted-by":"publisher","first-page":"771054","DOI":"10.3389\/fimmu.2021.771054","volume":"12","author":"JR Thomas","year":"2021","unstructured":"Thomas JR, Naidu P, Appios A, et al. The ontogeny and function of placental macrophages. Front Immunol. 2021;12:771054.","journal-title":"Front Immunol"},{"issue":"5\u20136","key":"7727_CR13","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1159\/000336717","volume":"4","author":"M Weidenbusch","year":"2012","unstructured":"Weidenbusch M, Anders HJ. Tissue microenvironments define and get reinforced by macrophage phenotypes in homeostasis or during inflammation, repair and fibrosis. J Innate Immun. 2012;4(5\u20136):463\u201377.","journal-title":"J Innate Immun"},{"issue":"5","key":"7727_CR14","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1002\/(SICI)1097-0029(19980901)42:5<351::AID-JEMT6>3.0.CO;2-S","volume":"42","author":"AL Watson","year":"1998","unstructured":"Watson AL, Burton GJ. A microscopical study of wound repair in the human placenta. Microsc Res Tech. 1998;42(5):351\u201368.","journal-title":"Microsc Res Tech"},{"key":"7727_CR15","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1016\/j.cbi.2018.07.008","volume":"92","author":"HH Hu","year":"2018","unstructured":"Hu HH, Chen DQ, Wang YN, et al. New insights into TGF-\u03b2\/Smad signaling in tissue fibrosis. Chem Biol Interact. 2018;92:76\u201383.","journal-title":"Chem Biol Interact"},{"key":"7727_CR16","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1016\/j.placenta.2016.06.003","volume":"44","author":"B Rahat","year":"2016","unstructured":"Rahat B, Thakur S, Bagga R, et al. Epigenetic regulation of STAT5A and its role as fetal DNA epigenetic marker during placental development and dysfunction. Placenta. 2016;44:46\u201353.","journal-title":"Placenta"},{"issue":"6","key":"7727_CR17","first-page":"4006","volume":"15","author":"X Wu","year":"2023","unstructured":"Wu X, Chen C, Han T, et al. Stat5a promotes Col10a1 gene expression during chondrocyte hypertrophic differentiation. Am J Transl Res. 2023;15(6):4006\u201319.","journal-title":"Am J Transl Res"},{"key":"7727_CR18","doi-asserted-by":"publisher","first-page":"180","DOI":"10.1016\/j.ejogrb.2018.10.041","volume":"231","author":"MJ Bicocca","year":"2018","unstructured":"Bicocca MJ, Sperling JD, Chauhan SP. Intrahepatic cholestasis of pregnancy: review of six national and regional guidelines. Eur J Obstet Gynecol Reprod Biol. 2018;231:180\u201387.","journal-title":"Eur J Obstet Gynecol Reprod Biol"},{"key":"7727_CR19","doi-asserted-by":"publisher","first-page":"e3799","DOI":"10.1136\/bmj.e3799","volume":"344","author":"LC Chappell","year":"2012","unstructured":"Chappell LC, Gurung V, Seed PT, et al. Ursodeoxycholic acid versus placebo, and early term delivery versus expectant management, in women with intrahepatic cholestasis of pregnancy: semifactorial randomised clinical trial. BMJ. 2012;344:e3799\u201399.","journal-title":"BMJ"},{"issue":"1","key":"7727_CR20","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1016\/j.ijgo.2013.02.015","volume":"122","author":"J Chen","year":"2013","unstructured":"Chen J, Deng W, Wang J, et al. Primary bile acids as potential biomarkers for the clinical grading of intrahepatic cholestasis of pregnancy. Int J Gynaecol Obstet. 2013;122(1):5\u20138.","journal-title":"Int J Gynaecol Obstet"},{"issue":"4","key":"7727_CR21","doi-asserted-by":"publisher","first-page":"1319","DOI":"10.1002\/hep.23469","volume":"51","author":"L Blaas","year":"2010","unstructured":"Blaas L, Kornfeld JW, Schramek D, et al. Disruption of the growth hormone-signal transducer and activator of transcription 5-insulinlike growth factor 1 axis severely aggravates liver fibrosis in a mouse model of cholestasis. Hepatology. 2010;51(4):1319\u201326.","journal-title":"Hepatology"},{"issue":"10174","key":"7727_CR22","doi-asserted-by":"publisher","first-page":"899","DOI":"10.1016\/S0140-6736(18)31877-4","volume":"393","author":"C Ovadia","year":"2019","unstructured":"Ovadia C, Seed PT, Sklavounos A, et al. Association of adverse perinatal outcomes of intrahepatic cholestasis of pregnancy with biochemical markers: results of aggregate and individual patient data meta-analyses. Lancet. 2019;393(10174):899\u2013909.","journal-title":"Lancet"},{"issue":"6","key":"7727_CR23","doi-asserted-by":"publisher","first-page":"2050","DOI":"10.1002\/hep.30975","volume":"71","author":"Y Liu","year":"2020","unstructured":"Liu Y, Chen K, Li F, et al. Probiotic lactobacillus rhamnosus GG prevents liver fibrosis through inhibiting hepatic bile acid synthesis and enhancing bile acid excretion in mice. Hepatology. 2020;71(6):2050\u201366.","journal-title":"Hepatology"},{"issue":"3","key":"7727_CR24","doi-asserted-by":"publisher","first-page":"526","DOI":"10.1016\/j.apsb.2018.11.004","volume":"9","author":"J Zhou","year":"2019","unstructured":"Zhou J, Huang N, Guo Y, et al. Combined obeticholic acid and apoptosis inhibitor treatment alleviates liver fibrosis. Acta Pharm Sin B. 2019;9(3):526\u201336.","journal-title":"Acta Pharm Sin B"},{"issue":"3","key":"7727_CR25","doi-asserted-by":"publisher","first-page":"634","DOI":"10.1016\/j.jhep.2021.03.029","volume":"75","author":"M Reich","year":"2021","unstructured":"Reich M, Spomer L, Klindt C, et al. Downregulation of TGR5 (GPBAR1) in biliary epithelial cells contributes to the pathogenesis of sclerosing cholangitis. J Hepatol. 2021;75(3):634\u201346.","journal-title":"J Hepatol"},{"issue":"11","key":"7727_CR26","doi-asserted-by":"publisher","first-page":"1819","DOI":"10.1681\/ASN.2010080793","volume":"21","author":"M Zeisberg","year":"2010","unstructured":"Zeisberg M, Neilson EG. Mechanisms of tubulointerstitial fibrosis. J Am Soc Nephrol. 2010;21(11):1819\u201334.","journal-title":"J Am Soc Nephrol"},{"issue":"7835","key":"7727_CR27","doi-asserted-by":"publisher","first-page":"555","DOI":"10.1038\/s41586-020-2938-9","volume":"587","author":"NC Henderson","year":"2020","unstructured":"Henderson NC, Rieder F, Wynn TA. Fibrosis: from mechanisms to medicines. Nature. 2020;587(7835):555\u201366.","journal-title":"Nature"},{"key":"7727_CR28","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1016\/j.bcp.2018.05.007","volume":"154","author":"H Lu","year":"2018","unstructured":"Lu H, Wu L, Liu L, et al. Quercetin ameliorates kidney injury and fibrosis by modulating M1\/M2 macrophage polarization. Biochem Pharmacol. 2018;154:203\u201312.","journal-title":"Biochem Pharmacol"},{"key":"7727_CR29","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1002\/(SICI)1097-0029(19980901)42:5<351::AID-JEMT6>3.0.CO;2-S","volume":"42","author":"AL Watson","year":"1998","unstructured":"Watson AL, Burton GJ. A microscopical study of wound repair in the human placenta. Microsc Res Tech. 1998;42:351\u201368.","journal-title":"Microsc Res Tech"},{"issue":"2","key":"7727_CR30","doi-asserted-by":"publisher","first-page":"709","DOI":"10.1016\/j.ajpath.2010.10.011","volume":"178","author":"D Schonkeren","year":"2011","unstructured":"Schonkeren D, van der Hoorn ML, Khedoe P, et al. Differential distribution and phenotype of decidual macrophages in preeclamptic versus control pregnancies. Am J Pathol. 2011;178(2):709\u201317.","journal-title":"Am J Pathol"},{"issue":"6","key":"7727_CR31","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1080\/14767050500141329","volume":"17","author":"MS Esplin","year":"2005","unstructured":"Esplin MS, Romero R, Chaiworapongsa T, et al. Monocyte chemotactic protein-1 is increased in the amniotic fluid of women who deliver preterm in the presence or absence of intra-amniotic infection. J Matern Fetal Neonatal Med. 2005;17(6):365\u201373.","journal-title":"J Matern Fetal Neonatal Med"},{"issue":"9","key":"7727_CR32","doi-asserted-by":"publisher","first-page":"2380","DOI":"10.4049\/jimmunol.1901185","volume":"204","author":"D Swieboda","year":"2020","unstructured":"Swieboda D, Johnson EL, Beaver J, et al. Baby\u2019s first macrophage: temporal regulation of Hofbauer cell phenotype influences ligand-mediated Innate immune responses across gestation. J Immunol. 2020;204(9):2380\u201391.","journal-title":"J Immunol"},{"key":"7727_CR33","doi-asserted-by":"publisher","first-page":"188","DOI":"10.1111\/j.1749-6632.1990.tb16111.x","volume":"593","author":"SM Wahl","year":"1990","unstructured":"Wahl SM, McCartney-Francis N, Allen JB, et al. Macrophage production of TGF-beta and regulation by TGF-beta. Ann N Y Acad Sci. 1990;593:188\u201396.","journal-title":"Ann N Y Acad Sci"},{"issue":"6","key":"7727_CR34","doi-asserted-by":"publisher","first-page":"1780","DOI":"10.1172\/JCI114362","volume":"84","author":"SL Friedman","year":"1989","unstructured":"Friedman SL, Arthur MJ. Activation of cultured rat hepatic lipocytes by Kupffer cell conditioned medium. Direct enhancement of matrix synthesis and stimulation of cell proliferation via induction of platelet-derived growth factor receptors. J Clin Invest. 1989;84(6):1780\u201385.","journal-title":"J Clin Invest"},{"issue":"40","key":"7727_CR35","doi-asserted-by":"publisher","first-page":"44508","DOI":"10.1021\/acsami.0c13839","volume":"12","author":"D Zhao","year":"2020","unstructured":"Zhao D, Cui W, Liu M, et al. Tetrahedral framework nucleic acid promotes the treatment of bisphosphonate-related osteonecrosis of the jaws by promoting angiogenesis and M2 polarization. ACS Appl Mater Interface. 2020;12(40):44508\u201322.","journal-title":"ACS Appl Mater Interface"},{"issue":"11","key":"7727_CR36","doi-asserted-by":"publisher","first-page":"e2203076","DOI":"10.1002\/adhm.202203076","volume":"12","author":"W Wang","year":"2023","unstructured":"Wang W, Xiao D, Lin L, et al. Antifibrotic effects of tetrahedral framework nucleic acids by inhibiting macrophage polarization and macrophage-myofibroblast transition in bladder remodeling. Adv Healthc Mater. 2023;12(11):e2203076.","journal-title":"Adv Healthc Mater"},{"issue":"3","key":"7727_CR37","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1038\/s41581-019-0110-2","volume":"15","author":"PM Tang","year":"2019","unstructured":"Tang PM, Nikolic-Paterson DJ, Lan HY. Macrophages: versatile players in renal inflammation and fibrosis. Nat Rev Nephrol. 2019;15(3):144\u201358.","journal-title":"Nat Rev Nephrol"},{"issue":"1","key":"7727_CR38","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1016\/j.ajhg.2011.11.016","volume":"90","author":"Y Yoneda","year":"2012","unstructured":"Yoneda Y, Haginoya K, Arai H, et al. De Novo and inherited mutations in COL4A2, encoding the type IV collagen \u03b12 chain cause porencephaly. Am J Hum Genet. 2012;90(1):86\u201390.","journal-title":"Am J Hum Genet"},{"issue":"6","key":"7727_CR39","doi-asserted-by":"publisher","first-page":"703","DOI":"10.1038\/s41589-022-01248-4","volume":"19","author":"A Kaneshige","year":"2023","unstructured":"Kaneshige A, Bai L, Wang M, et al. A selective small-molecule STAT5 PROTAC degrader capable of achieving tumor regression in vivo. Nat Chem Biol. 2023;19(6):703\u201311.","journal-title":"Nat Chem Biol"},{"issue":"8","key":"7727_CR40","doi-asserted-by":"publisher","first-page":"611","DOI":"10.1038\/nchembio.1858","volume":"11","author":"DP Bondeson","year":"2015","unstructured":"Bondeson DP, Mares A, Smith IE, et al. Catalytic in vivo protein knockdown by small-molecule PROTACs. Nat Chem Biol. 2015;11(8):611\u201317.","journal-title":"Nat Chem Biol"},{"issue":"1","key":"7727_CR41","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1016\/j.chembiol.2017.09.010","volume":"25","author":"DP Bondeson","year":"2018","unstructured":"Bondeson DP, Smith BE, Burslem GM, et al. Lessons in PROTAC design from selective degradation with a promiscuous warhead. Cell Chem Biol. 2018;25(1):78\u201387.e5.","journal-title":"Cell Chem Biol"}],"container-title":["Journal of Translational Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12967-026-07727-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12967-026-07727-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12967-026-07727-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T17:01:54Z","timestamp":1774026114000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s12967-026-07727-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,13]]},"references-count":41,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["7727"],"URL":"https:\/\/doi.org\/10.1186\/s12967-026-07727-9","relation":{},"ISSN":["1479-5876"],"issn-type":[{"value":"1479-5876","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,13]]},"assertion":[{"value":"17 August 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 December 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 February 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The present study was approved by the ethical committee of the First Affiliated Hospital of Chongqing Medical University (Ethical Application Ref: 2023\u2013373). All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. All participants signed a written informed consent form prior to their participation in this study.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"395"}}