{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T13:37:52Z","timestamp":1787665072904,"version":"build-2736575974"},"reference-count":46,"publisher":"Elsevier BV","issue":"8","license":[{"start":{"date-parts":[[2024,8,1]],"date-time":"2024-08-01T00:00:00Z","timestamp":1722470400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2024,8,1]],"date-time":"2024-08-01T00:00:00Z","timestamp":1722470400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,8,7]],"date-time":"2025-08-07T00:00:00Z","timestamp":1754524800000},"content-version":"vor","delay-in-days":371,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2019YFC1315900"],"award-info":[{"award-number":["2019YFC1315900"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2019YFC1315802"],"award-info":[{"award-number":["2019YFC1315802"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82170659"],"award-info":[{"award-number":["82170659"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81872043"],"award-info":[{"award-number":["81872043"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["cell.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Molecular Therapy"],"published-print":{"date-parts":[[2024,8]]},"DOI":"10.1016\/j.ymthe.2024.06.030","type":"journal-article","created":{"date-parts":[[2024,7,2]],"date-time":"2024-07-02T02:49:30Z","timestamp":1719888570000},"page":"2624-2640","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":17,"title":["Optimized rAAV8 targeting acinar KLF4 ameliorates fibrosis in chronic pancreatitis via exosomes-enriched let-7s suppressing pancreatic stellate cells activation"],"prefix":"10.1016","volume":"32","author":[{"given":"Yating","family":"Zhao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongpu","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengyuan","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayu","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingxiao","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenbo","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiulin","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaoshen","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fanyang","family":"Kong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiqi","family":"Du","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7515-2613","authenticated-orcid":false,"given":"Xiangyu","family":"Kong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ymthe.2024.06.030_bib1","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1016\/S0140-6736(20)31318-0","article-title":"Chronic pancreatitis","volume":"396","author":"Beyer","year":"2020","journal-title":"Lancet"},{"key":"10.1016\/j.ymthe.2024.06.030_bib2","doi-asserted-by":"crossref","first-page":"382","DOI":"10.3748\/wjg.v23.i3.382","article-title":"Pancreatic stellate cell: Pandora\u2019s box for pancreatic disease biology","volume":"23","author":"Bynigeri","year":"2017","journal-title":"World J. Gastroenterol."},{"key":"10.1016\/j.ymthe.2024.06.030_bib3","doi-asserted-by":"crossref","first-page":"S48","DOI":"10.1016\/j.cgh.2009.07.038","article-title":"Roles of pancreatic stellate cells in pancreatic inflammation and fibrosis","volume":"7","author":"Masamune","year":"2009","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"10.1016\/j.ymthe.2024.06.030_bib4","doi-asserted-by":"crossref","first-page":"461","DOI":"10.2147\/JIR.S299298","article-title":"Regulation of Pancreatic Fibrosis by Acinar Cell-Derived Exosomal miR-130a-3p via Targeting of Stellate Cell PPAR-\u03b3","volume":"14","author":"Wang","year":"2021","journal-title":"J.\u00a0Inflamm. Res."},{"key":"10.1016\/j.ymthe.2024.06.030_bib5","doi-asserted-by":"crossref","DOI":"10.1126\/science.aau6977","article-title":"The biology, function, and biomedical applications of exosomes","volume":"367","author":"Kalluri","year":"2020","journal-title":"Science"},{"key":"10.1016\/j.ymthe.2024.06.030_bib6","doi-asserted-by":"crossref","first-page":"950","DOI":"10.1136\/gutjnl-2018-316627","article-title":"VDR signaling inhibits cancer-associated-fibroblasts\u2019 release of exosomal miR-10a-5p and limits their supportive effects on pancreatic cancer cells","volume":"68","author":"Kong","year":"2019","journal-title":"Gut"},{"key":"10.1016\/j.ymthe.2024.06.030_bib7","doi-asserted-by":"crossref","first-page":"1457","DOI":"10.1038\/nbt1372","article-title":"Endogenous microRNA can be broadly exploited to regulate transgene expression according to tissue, lineage and differentiation state","volume":"25","author":"Brown","year":"2007","journal-title":"Nat. Biotechnol."},{"key":"10.1016\/j.ymthe.2024.06.030_bib8","doi-asserted-by":"crossref","first-page":"7179","DOI":"10.1038\/s41467-021-27499-8","article-title":"Distinct roles of KLF4 in mesenchymal cell subtypes during lung fibrogenesis","volume":"12","author":"Chandran","year":"2021","journal-title":"Nat. Commun."},{"key":"10.1016\/j.ymthe.2024.06.030_bib9","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-017-14602-7","article-title":"Kr\u00fcpple-like-factor 4 Attenuates Lung Fibrosis via Inhibiting Epithelial-mesenchymal Transition","volume":"7","author":"Lin","year":"2017","journal-title":"Sci. Rep."},{"key":"10.1016\/j.ymthe.2024.06.030_bib10","doi-asserted-by":"crossref","first-page":"1837","DOI":"10.1007\/s11255-023-03503-6","article-title":"MiR-449a downregulation alleviates the progression of renal interstitial fibrosis by mediating the KLF4\/MFN2 axis","volume":"55","author":"Fang","year":"2023","journal-title":"Int. Urol. Nephrol."},{"key":"10.1016\/j.ymthe.2024.06.030_bib11","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1038\/s41401-020-0463-x","article-title":"KLF4 initiates sustained YAP activation to promote renal fibrosis in mice after ischemia-reperfusion kidney injury","volume":"42","author":"Xu","year":"2021","journal-title":"Acta Pharmacol. Sin."},{"key":"10.1016\/j.ymthe.2024.06.030_bib12","doi-asserted-by":"crossref","first-page":"327","DOI":"10.3389\/fphys.2015.00327","article-title":"The Role of Kr\u00fcppel-like Factor 4 in Renal Fibrosis","volume":"6","author":"Ke","year":"2015","journal-title":"Front. Physiol."},{"key":"10.1016\/j.ymthe.2024.06.030_bib13","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1038\/s41419-020-03296-x","article-title":"ATF4-mediated histone deacetylase HDAC1 promotes the progression of acute pancreatitis","volume":"12","author":"Deng","year":"2021","journal-title":"Cell Death Dis."},{"key":"10.1016\/j.ymthe.2024.06.030_bib14","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1538\/expanim.22-0147","article-title":"The Kruppel-like factor 4-signal transducer and activator of transcription 5A axis promotes pancreatic fibrosis in mice with caerulein-induced chronic pancreatitis","volume":"72","author":"Wang","year":"2023","journal-title":"Exp. Anim."},{"key":"10.1016\/j.ymthe.2024.06.030_bib15","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1038\/nrgastro.2017.12","article-title":"Acinar cell plasticity and development of pancreatic ductal adenocarcinoma","volume":"14","author":"Storz","year":"2017","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"10.1016\/j.ymthe.2024.06.030_bib16","doi-asserted-by":"crossref","first-page":"9946","DOI":"10.3390\/ijms24129946","article-title":"Acinar-to-Ductal Metaplasia (ADM): On the Road to Pancreatic Intraepithelial Neoplasia (PanIN) and Pancreatic Cancer","volume":"24","author":"Marstrand-Dauc\u00e9","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.ymthe.2024.06.030_bib17","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1016\/j.ccell.2016.02.005","article-title":"KLF4 Is Essential for Induction of Cellular Identity Change and Acinar-to-Ductal Reprogramming during Early Pancreatic Carcinogenesis","volume":"29","author":"Wei","year":"2016","journal-title":"Cancer Cell"},{"key":"10.1016\/j.ymthe.2024.06.030_bib18","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1038\/s41573-019-0012-9","article-title":"Adeno-associated virus vector as a platform for gene therapy delivery","volume":"18","author":"Wang","year":"2019","journal-title":"Nat. Rev. Drug Discov."},{"key":"10.1016\/j.ymthe.2024.06.030_bib19","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1007\/s40259-017-0234-5","article-title":"Adeno-Associated Virus (AAV) as a Vector for Gene Therapy","volume":"31","author":"Naso","year":"2017","journal-title":"BioDrugs."},{"key":"10.1016\/j.ymthe.2024.06.030_bib20","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1089\/hgtb.2016.089","article-title":"Efficient Gene Delivery and Expression in Pancreas and Pancreatic Tumors by Capsid-Optimized AAV8 Vectors","volume":"28","author":"Chen","year":"2017","journal-title":"Hum. Gene Ther. Methods"},{"key":"10.1016\/j.ymthe.2024.06.030_bib21","doi-asserted-by":"crossref","DOI":"10.34133\/2022\/9784081","article-title":"Activation of Pancreatic Acinar FXR Protects against Pancreatitis via Osgin1-Mediated Restoration of Efficient Autophagy","volume":"2022","author":"Zheng","year":"2022","journal-title":"Research"},{"key":"10.1016\/j.ymthe.2024.06.030_bib22","doi-asserted-by":"crossref","first-page":"756","DOI":"10.1136\/gut.25.7.756","article-title":"Classification of pancreatitis","volume":"25","author":"Sarner","year":"1984","journal-title":"Gut"},{"key":"10.1016\/j.ymthe.2024.06.030_bib23","doi-asserted-by":"crossref","first-page":"2226","DOI":"10.1136\/gutjnl-2017-315778","article-title":"Exosomal adrenomedullin derived from cancer-associated fibroblasts promotes lipolysis in adipose tissue","volume":"67","author":"Kong","year":"2018","journal-title":"Gut"},{"key":"10.1016\/j.ymthe.2024.06.030_bib24","article-title":"Updating MISEV: Evolving the minimal requirements for studies of extracellular vesicles","volume":"10","author":"Witwer","year":"2021","journal-title":"J.\u00a0Extracell. Vesicles"},{"key":"10.1016\/j.ymthe.2024.06.030_bib25","doi-asserted-by":"crossref","first-page":"2362","DOI":"10.1016\/j.bbadis.2015.08.010","article-title":"Blockade of exosome generation with GW4869 dampens the sepsis-induced inflammation and cardiac dysfunction","volume":"1852","author":"Essandoh","year":"2015","journal-title":"Biochim. Biophys. Acta"},{"key":"10.1016\/j.ymthe.2024.06.030_bib26","article-title":"Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines","volume":"7","author":"Th\u00e9ry","year":"2018","journal-title":"J.\u00a0Extracell. Vesicles"},{"key":"10.1016\/j.ymthe.2024.06.030_bib27","doi-asserted-by":"crossref","DOI":"10.1002\/smll.202200060","article-title":"Sustained Exosome-Guided Macrophage Polarization Using Hydrolytically Degradable PEG Hydrogels for Cutaneous Wound Healing: Identification of Key Proteins and MiRNAs, and Sustained Release Formulation","volume":"18","author":"Kwak","year":"2022","journal-title":"Small"},{"key":"10.1016\/j.ymthe.2024.06.030_bib28","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1038\/s41420-023-01416-y","article-title":"KLF4 transcription factor in tumorigenesis","volume":"9","author":"He","year":"2023","journal-title":"Cell Death Discov."},{"key":"10.1016\/j.ymthe.2024.06.030_bib29","doi-asserted-by":"crossref","DOI":"10.1093\/ofid\/ofy268","article-title":"Circulating let-7 Levels in Serum Correlate With the Severity of Hepatic Fibrosis in Chronic Hepatitis C","volume":"5","author":"Matsuura","year":"2018","journal-title":"Open Forum Infect. Dis."},{"key":"10.1016\/j.ymthe.2024.06.030_bib30","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pntd.0009472","article-title":"The role of let-7b in the inhibition of hepatic stellate cell activation by rSjP40","volume":"15","author":"Sun","year":"2021","journal-title":"PLoS Negl. Trop. Dis."},{"key":"10.1016\/j.ymthe.2024.06.030_bib31","doi-asserted-by":"crossref","DOI":"10.1155\/2019\/4506303","article-title":"Exosomal miRNA Let-7 from Menstrual Blood-Derived Endometrial Stem Cells Alleviates Pulmonary Fibrosis through Regulating Mitochondrial DNA Damage","volume":"2019","author":"Sun","year":"2019","journal-title":"Oxid. Med. Cell. Longev."},{"key":"10.1016\/j.ymthe.2024.06.030_bib32","doi-asserted-by":"crossref","first-page":"1290","DOI":"10.1038\/mt.2016.90","article-title":"Mesenchymal Stem Cells Deliver Exogenous MicroRNA-let7c via Exosomes to Attenuate Renal Fibrosis","volume":"24","author":"Wang","year":"2016","journal-title":"Mol. Ther."},{"key":"10.1016\/j.ymthe.2024.06.030_bib33","doi-asserted-by":"crossref","DOI":"10.3389\/fphys.2022.937878","article-title":"The Smad3-dependent microRNA let-7i-5p promoted renal fibrosis in mice with unilateral ureteral obstruction","volume":"13","author":"Peng","year":"2022","journal-title":"Front. Physiol."},{"key":"10.1016\/j.ymthe.2024.06.030_bib34","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1152\/physiolgenomics.00039.2017","article-title":"Therapeutic potential of microRNAs for the treatment of renal fibrosis and CKD","volume":"50","author":"Lv","year":"2018","journal-title":"Physiol. Genomics"},{"key":"10.1016\/j.ymthe.2024.06.030_bib35","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1016\/j.cell.2011.10.039","article-title":"Lin28A and Lin28B inhibit let-7 microRNA biogenesis by distinct mechanisms","volume":"147","author":"Piskounova","year":"2011","journal-title":"Cell"},{"key":"10.1016\/j.ymthe.2024.06.030_bib36","doi-asserted-by":"crossref","first-page":"5586","DOI":"10.3390\/molecules28145586","article-title":"Pancreatic Stellate Cells and the Targeted Therapeutic Strategies in Chronic Pancreatitis","volume":"28","author":"Chang","year":"2023","journal-title":"Molecules"},{"key":"10.1016\/j.ymthe.2024.06.030_bib37","doi-asserted-by":"crossref","first-page":"1488","DOI":"10.1053\/j.gastro.2023.08.029","article-title":"Pancreatic acinar cells-derived sphingosine-1-phosphate contributes to fibrosis of chronic pancreatitis via inducing autophagy and activation of pancreatic stellate cells","volume":"165","author":"Wang","year":"2023","journal-title":"Gastroenterology"},{"key":"10.1016\/j.ymthe.2024.06.030_bib38","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1016\/j.ccr.2011.01.001","article-title":"Identification of miRNomes in human liver and hepatocellular carcinoma reveals miR-199a\/b-3p as therapeutic target for hepatocellular carcinoma","volume":"19","author":"Hou","year":"2011","journal-title":"Cancer Cell"},{"key":"10.1016\/j.ymthe.2024.06.030_bib39","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1016\/j.tcb.2008.07.007","article-title":"The let-7 family of microRNAs","volume":"18","author":"Roush","year":"2008","journal-title":"Trends Cell Biol."},{"key":"10.1016\/j.ymthe.2024.06.030_bib40","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1136\/gut.43.1.128","article-title":"Periacinar stellate shaped cells in rat pancreas: identification, isolation, and culture","volume":"43","author":"Apte","year":"1998","journal-title":"Gut"},{"key":"10.1016\/j.ymthe.2024.06.030_bib41","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1186\/s12951-023-01942-y","article-title":"Mesenchymal stem cell-derived exosomal miR-27b-3p alleviates liver fibrosis via downregulating YAP\/LOXL2 pathway","volume":"21","author":"Cheng","year":"2023","journal-title":"J.\u00a0Nanobiotechnol."},{"key":"10.1016\/j.ymthe.2024.06.030_bib42","doi-asserted-by":"crossref","first-page":"D165","DOI":"10.1093\/nar\/gkab1113","article-title":"JASPAR 2022: the 9th release of the open-access database of transcription factor binding profiles","volume":"50","author":"Castro-Mondragon","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.ymthe.2024.06.030_bib43","doi-asserted-by":"crossref","first-page":"D1188","DOI":"10.1093\/nar\/gkac1072","article-title":"The UCSC Genome Browser database: 2023 update","volume":"51","author":"Nassar","year":"2023","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.ymthe.2024.06.030_bib44","doi-asserted-by":"crossref","first-page":"D991","DOI":"10.1093\/nar\/gks1193","article-title":"NCBI GEO: archive for functional genomics data sets--update","volume":"41","author":"Barrett","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.ymthe.2024.06.030_bib45","doi-asserted-by":"crossref","first-page":"1.30.1","DOI":"10.1002\/cpbi.5","article-title":"The GeneCards Suite: From Gene Data Mining to Disease Genome Sequence Analyses","volume":"54","author":"Stelzer","year":"2016","journal-title":"Curr. Protoc. Bioinf."},{"key":"10.1016\/j.ymthe.2024.06.030_bib46","doi-asserted-by":"crossref","first-page":"e47","DOI":"10.1093\/nar\/gkv007","article-title":"limma powers differential expression analyses for RNA-sequencing and microarray studies","volume":"43","author":"Ritchie","year":"2015","journal-title":"Nucleic Acids Res."}],"container-title":["Molecular Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1525001624004131?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1525001624004131?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,11,22]],"date-time":"2025-11-22T02:53:32Z","timestamp":1763780012000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1525001624004131"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8]]},"references-count":46,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2024,8]]}},"alternative-id":["S1525001624004131"],"URL":"https:\/\/doi.org\/10.1016\/j.ymthe.2024.06.030","relation":{},"ISSN":["1525-0016"],"issn-type":[{"value":"1525-0016","type":"print"}],"subject":[],"published":{"date-parts":[[2024,8]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Optimized rAAV8 targeting acinar KLF4 ameliorates fibrosis in chronic pancreatitis via exosomes-enriched let-7s suppressing pancreatic stellate cells activation","name":"articletitle","label":"Article Title"},{"value":"Molecular Therapy","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ymthe.2024.06.030","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2024 The American Society of Gene and Cell Therapy. Published by Elsevier Inc.","name":"copyright","label":"Copyright"}]}}