{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T20:23:48Z","timestamp":1791318228251,"version":"4.3.1"},"reference-count":43,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2023,6,26]],"date-time":"2023-06-26T00:00:00Z","timestamp":1687737600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82170762"],"award-info":[{"award-number":["82170762"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003453","name":"Natural Science Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2022A1515012637"],"award-info":[{"award-number":["2022A1515012637"]}],"id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Extracellular Vesicle"],"published-print":{"date-parts":[[2023,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Progressive peritoneal fibrosis and the loss of peritoneal function often emerged in patients undergoing long\u2010term peritoneal dialysis (PD), resulting in PD therapy failure. Varieties of cell\u2010cell communications among peritoneal cells play a significant role in peritoneal fibrogenesis. Extracellular vesicles (EVs) have been confirmed to involve in intercellular communication by transmitting proteins, nucleic acids or lipids. However, their roles and functional mechanisms in peritoneal fibrosis remain to be determined. Using integrative analysis of EV proteomics and single\u2010cell RNA sequencing, we characterized the EVs isolated from PD patient's effluent and revealed that mesothelial cells are the main source of EVs in PD effluent. We demonstrated that transforming growth factor\u2010\u03b21 (TGF\u2010\u03b21) can substitute for PD fluid to stimulate mesothelial cells releasing EVs, which in turn promoted fibroblast activation and peritoneal fibrogenesis. Blockade of EVs secretion by GW4869 or Rab27a knockdown markedly suppressed PD\u2010induced fibroblast activation and peritoneal fibrosis. Mechanistically, injured mesothelial cells produced EVs containing high level of integrin\u2010linked kinase (ILK), which was delivered to fibroblast and activated them via p38 MAPK signalling pathway. Clinically, the expression of ILK was up\u2010regulated in fibrotic peritoneum of patients undergoing long\u2010term PD. The percentage of ILK positive EVs in PD effluent correlated with peritoneal dysfunction and the degree of peritoneal damage. Our study highlights that peritoneal EVs mediate communications between mesothelial cells and fibroblasts to initiate peritoneal fibrogenesis. Targeting EVs or ILK could provide a novel therapeutic strategy to combat peritoneal fibrosis.<\/jats:p>","DOI":"10.1002\/jev2.12334","type":"journal-article","created":{"date-parts":[[2023,6,26]],"date-time":"2023-06-26T03:56:00Z","timestamp":1687751760000},"source":"Crossref","is-referenced-by-count":45,"title":["Extracellular vesicle\u2010packaged ILK from mesothelial cells promotes fibroblast activation in peritoneal fibrosis"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2052-1140","authenticated-orcid":false,"given":"Qiang","family":"Huang","sequence":"first","affiliation":[{"name":"Nephrology Division, Department of Medicine the Third Affiliated Hospital, Sun Yat\u2010sen University Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxiang","family":"Sun","sequence":"additional","affiliation":[{"name":"Nephrology Division, Department of Medicine the Third Affiliated Hospital, Sun Yat\u2010sen University Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Long","family":"Peng","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Department of Medicine the Third Affiliated Hospital, Sun Yat\u2010sen University Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Sun","sequence":"additional","affiliation":[{"name":"Nephrology Division, Department of Medicine the Third Affiliated Hospital, Sun Yat\u2010sen University Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zixin","family":"Sha","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences Carnegie Mellon University Pittsburg Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongchun","family":"Lin","sequence":"additional","affiliation":[{"name":"Nephrology Division, Department of Medicine the Third Affiliated Hospital, Sun Yat\u2010sen University Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongjie","family":"Li","sequence":"additional","affiliation":[{"name":"Nephrology Division, Department of Medicine the Third Affiliated Hospital, Sun Yat\u2010sen University Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Canming","family":"Li","sequence":"additional","affiliation":[{"name":"Nephrology Division, Department of Medicine the Third Affiliated Hospital, Sun Yat\u2010sen University Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiqun","family":"Li","sequence":"additional","affiliation":[{"name":"Nephrology Division, Department of Medicine the Third Affiliated Hospital, Sun Yat\u2010sen University Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongli","family":"Shang","sequence":"additional","affiliation":[{"name":"Nephrology Division, Department of Medicine the Third Affiliated Hospital, Sun Yat\u2010sen University Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanxu","family":"Chen","sequence":"additional","affiliation":[{"name":"Organ Transplant Center the First Affiliated Hospital, Sun Yat\u2010sen University Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianrui","family":"Dou","sequence":"additional","affiliation":[{"name":"Department of Nephrology Shunde Hospital, Southern Medical University (The First People's Hospital of Shunde) Foshan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaoyong","family":"Hu","sequence":"additional","affiliation":[{"name":"Nephrology Division, Department of Medicine Baylor College of Medicine Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zengchun","family":"Ye","sequence":"additional","affiliation":[{"name":"Nephrology Division, Department of Medicine the Third Affiliated Hospital, Sun Yat\u2010sen University Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Peng","sequence":"additional","affiliation":[{"name":"Nephrology Division, Department of Medicine the Third Affiliated Hospital, Sun Yat\u2010sen University Guangzhou China"},{"name":"NHC Key Laboratory of Clinical Nephrology (Sun Yat\u2010sen University) and Guangdong Provincial Key Laboratory of Nephrology Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,6,26]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/ki.1997.25"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-00324-4"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2013101079"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells8040330"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneph.2016.54"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.824278"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2018.12.030"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2020.05.004"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2021.05.026"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2018.01815"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aaz8697"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2008090930"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2019.11.026"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2014.2162"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41418-019-0349-y"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneph.2017.148"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2021.09.002"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.12089"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep01144"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-022-00460-3"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb2000"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2021-324994"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.120.052009"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrev.7b00534"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.5987"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-22-0569"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aav5341"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00464-013-2801-2"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra2100152"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2014.04.030"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2020.07.014"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.62046"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/jev2.12064"},{"key":"e_1_2_8_35_1","article-title":"New developments in peritoneal fibroblast biology: Implications for inflammation and fibrosis in peritoneal dialysis","author":"Witowski J.","year":"2015","journal-title":"BioMed 2019Research International"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa020809"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-019-0990-6"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2020.12.019"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1159\/000490821"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.119.315829"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-022-04506-4"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1002\/ctm2.321"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-021-04363-7"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.21315"}],"container-title":["Journal of Extracellular Vesicles"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/isevjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jev2.12334","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T16:06:39Z","timestamp":1760630799000},"score":1,"resource":{"primary":{"URL":"https:\/\/isevjournals.onlinelibrary.wiley.com\/doi\/10.1002\/jev2.12334"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,6,26]]},"references-count":43,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2023,7]]}},"alternative-id":["10.1002\/jev2.12334"],"URL":"https:\/\/doi.org\/10.1002\/jev2.12334","archive":["Portico"],"relation":{},"ISSN":["2001-3078","2001-3078"],"issn-type":[{"value":"2001-3078","type":"print"},{"value":"2001-3078","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,6,26]]},"article-number":"12334"}}