{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T20:23:24Z","timestamp":1790886204431,"version":"4.1.0"},"reference-count":56,"publisher":"Wiley","issue":"48","license":[{"start":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T00:00:00Z","timestamp":1760313600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T00:00:00Z","timestamp":1760313600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81704084"],"award-info":[{"award-number":["81704084"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Postoperative peritoneal adhesion (PPA) develops through TGF\u2010\u03b21\u2010driven fibrotic remodeling, characterized by neutrophil extracellular trap (NETs)\u2010induced aberrant epithelial\u2010to\u2010mesenchymal transition (EMT) deposition. Although aloe\u2010emodin (AE) exhibits anti\u2010fibrosis potential, its molecular mechanisms remain elusive. Forkhead box protein C2 (FOXC2) is a critical regulator of fibrotic tissue formation, yet its role in PPA is unknown. Here, it is demonstrated that FOXC2 expression is elevated in human ileostomy tissue, PPA rodent model, and TGF\u2010\u03b21\u2010exposed peritoneal mesothelial cells (PMCs), where it orchestrates NETs formation and extracellular matrix (ECM) remodeling. Mechanically, CRISPR\/Cas\u2010based knockdown and overexpression of FOXC2 alter EMT changes in PMCs, which is achieved via TGF\u2010\u03b21\u2010Smad2\/3 signaling. FOXC2 functions as a dual mediator and amplifier through the TGF\u2010\u03b21\u2010Smad2\/3 pathway feedback loop to drive EMT alterations. Its overexpression further induces neutrophil recruitment and NETs formation, exacerbating EMT in PMCs. Notably, AE ameliorates FOXC2\u2010driven peritoneal fibrosis by impeding NETs formation and EMT changes through the TGF\u2010\u03b21\u2010Smad2\/3 pathway. Moreover, AE binds directly to FOXC2, and the Ser125 residue is critical for the binding of FOXC2 to AE. These findings identify FOXC2 as a pivotal effector in fibrotic responses during PPA formation and reveal that AE targeting the Ser125 residue of FOXC2 may be a promising therapeutic approach to attenuate PPA.<\/jats:p>","DOI":"10.1002\/advs.202511013","type":"journal-article","created":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T03:10:51Z","timestamp":1760411451000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Aloe\u2010Emodin Targeting FOXC2 Disrupts NETs Formation and EMT\u2010Driven Postoperative Peritoneal Adhesion Through TGF\u2010\u03b21\u2010Smad2\/3 Pathway"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5220-3094","authenticated-orcid":false,"given":"Lili","family":"Yang","sequence":"first","affiliation":[{"name":"Jiangsu Provincial Engineering Research Center of TCM External Medication Development and Application Nanjing University of Chinese Medicine  Nanjing 210023 China"},{"name":"Jingwen Library Nanjing University of Chinese Medicine  Nanjing 210023 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunda","family":"Fang","sequence":"additional","affiliation":[{"name":"School of First Clinical Medicine Nanjing University of Chinese Medicine  Nanjing 210023 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuheng","family":"Lian","sequence":"additional","affiliation":[{"name":"Faculty of Chinese Medicine Macau University of Science and Technology  Taipa Macau 999078 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyang","family":"Kong","sequence":"additional","affiliation":[{"name":"School of Health Preservation and Rehabilitation Nanjing University of Chinese Medicine  Nanjing 210023 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Miao","sequence":"additional","affiliation":[{"name":"School of First Clinical Medicine Nanjing University of Chinese Medicine  Nanjing 210023 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanqi","family":"Chen","sequence":"additional","affiliation":[{"name":"School of First Clinical Medicine Nanjing University of Chinese Medicine  Nanjing 210023 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Li","sequence":"additional","affiliation":[{"name":"School of Health Preservation and Rehabilitation Nanjing University of Chinese Medicine  Nanjing 210023 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feiyan","family":"Chen","sequence":"additional","affiliation":[{"name":"Research and Innovation Center College of Traditional Chinese Medicine Integrated Chinese and Western Medicine College Nanjing University of Chinese Medicine  Nanjing 210023 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Ningbo Municipal Hospital of TCM Affiliated Hospital of Zhejiang Chinese Medical University  Ningbo 315012 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Pharmacy Nanjing University of Chinese Medicine  Nanjing 210023 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9968-2501","authenticated-orcid":false,"given":"Yaoyao","family":"Bian","sequence":"additional","affiliation":[{"name":"School of Health Preservation and Rehabilitation Nanjing University of Chinese Medicine  Nanjing 210023 China"},{"name":"TCM Rehabilitation Center Jiangsu Second Chinese Medicine Hospital  Nanjing 210023 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,10,13]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1097\/DCR.0000000000000405"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/humupd\/7.6.556"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202470131"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm12041351"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(19)32636-4"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(13)61687-6"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13017-016-0109-y"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2482-11-13"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11655-023-3735-0"},{"key":"e_1_2_9_10_1","first-page":"272","volume":"23","author":"Lili Yang L. Z.","year":"2019","journal-title":"Chinese J. Tissue Eng. Res."},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.54403"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells13110991"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2023.108289"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.663303"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/wrr.12203"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.matbio.2016.01.017"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijsu.2015.06.081"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2009.397"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.4161\/cc.9.12.12050"},{"key":"e_1_2_9_20_1","first-page":"1","volume":"15","author":"Yang L.","year":"2024","journal-title":"Front. Immunol."},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1155\/2019\/1769374"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.2174\/0113895575298364240409064833"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms241813929"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jafc.4c00969"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom12101498"},{"key":"e_1_2_9_26_1","first-page":"54","volume":"214","author":"Li S.","year":"2024","journal-title":"Biol. Med."},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2023.117242"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2023.129369"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2010.01.017"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20050591"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneph.2016.48"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1067\/msy.2001.113039"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2004.03.008"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.5860"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-023-45617-y"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2024.1427113"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-024-07820-3"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12931-025-03150-8"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0703900104"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00123.2011"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-017-3827-y"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1158\/1541-7786.MCR-10-0004"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.3892\/or.2014.3119"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1186\/s41236-017-0005-8"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcancer.2022.09.004"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2024.112516"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mtbio.2025.101637"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1155\/2022\/9226022"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2024.118290"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11030-022-10519-0"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.4251\/wjgo.v12.i1.54"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpba.2010.08.022"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1080\/00015458.2010.11680568"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0039-6060(96)80096-1"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0015-0282(99)00368-4"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000035350"}],"container-title":["Advanced Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202511013","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/advs.202511013","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202511013","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,15]],"date-time":"2026-08-15T18:08:49Z","timestamp":1786817329000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/advs.202511013"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,13]]},"references-count":56,"journal-issue":{"issue":"48","published-print":{"date-parts":[[2025,12]]}},"alternative-id":["10.1002\/advs.202511013"],"URL":"https:\/\/doi.org\/10.1002\/advs.202511013","archive":["Portico"],"relation":{},"ISSN":["2198-3844","2198-3844"],"issn-type":[{"value":"2198-3844","type":"print"},{"value":"2198-3844","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,13]]},"assertion":[{"value":"2025-06-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-13","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e11013"}}