{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T06:40:09Z","timestamp":1790750409902,"version":"4.1.0"},"reference-count":36,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2016,7]]},"abstract":"<jats:p>\n                    Liver fibrosis is a common outcome of chronic liver disease that leads to liver cirrhosis and hepatocellular carcinoma. No US Food and Drug Administration\u2013approved targeted antifibrotic therapy exists. Activated hepatic stellate cells (aHSCs) are the major cell types responsible for liver fibrosis; therefore, eradication of aHSCs, while preserving quiescent HSCs and other normal cells, is a logical strategy to stop and\/or reverse liver fibrogenesis\/fibrosis. However, there are no effective approaches to specifically deplete aHSCs during fibrosis without systemic toxicity. aHSCs are associated with elevated expression of death receptors and become sensitive to tumor necrosis factor\u2013related apoptosis\u2010inducing ligand (TRAIL)\u2010induced cell death. Treatment with recombinant TRAIL could be a potential strategy to ameliorate liver fibrosis; however, the therapeutic application of recombinant TRAIL is halted due to its very short half\u2010life. To overcome this problem, we previously generated PEGylated TRAIL (TRAIL\n                    <jats:sub>PEG<\/jats:sub>\n                    ) that has a much longer half\u2010life in rodents than native\u2010type TRAIL. In this study, we demonstrate that intravenous TRAIL\n                    <jats:sub>PEG<\/jats:sub>\n                    has a markedly extended half\u2010life over native\u2010type TRAIL in nonhuman primates and has no toxicity in primary human hepatocytes. Intravenous injection of TRAIL\n                    <jats:sub>PEG<\/jats:sub>\n                    directly induces apoptosis of aHSCs\n                    <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                    and ameliorates carbon tetrachloride\u2010induced fibrosis\/cirrhosis in rats by simultaneously down\u2010regulating multiple key fibrotic markers that are associated with aHSCs.\n                    <jats:italic toggle=\"yes\">Conclusion<\/jats:italic>\n                    : TRAIL\u2010based therapies could serve as new therapeutics for liver fibrosis\/cirrhosis and possibly other fibrotic diseases. (H\n                    <jats:sc>epatology<\/jats:sc>\n                    2016;64:209\u2013223)\n                  <\/jats:p>","DOI":"10.1002\/hep.28432","type":"journal-article","created":{"date-parts":[[2015,12,28]],"date-time":"2015-12-28T18:19:06Z","timestamp":1451326746000},"page":"209-223","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":70,"title":["Systemic PEGylated TRAIL treatment ameliorates liver cirrhosis in rats by eliminating activated hepatic stellate cells"],"prefix":"10.1097","volume":"64","author":[{"given":"Yumin","family":"Oh","sequence":"first","affiliation":[{"name":"The Russell H. Morgan Department of Radiology and Radiological Science,Johns Hopkins University School of Medicine,Baltimore,MD"},{"name":"The Center for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine,Baltimore,MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ogyi","family":"Park","sequence":"additional","affiliation":[{"name":"The Russell H. Morgan Department of Radiology and Radiological Science,Johns Hopkins University School of Medicine,Baltimore,MD"},{"name":"The Center for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine,Baltimore,MD"},{"name":"Laboratory of Liver Diseases,National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health,Bethesda,MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalena","family":"Swierczewska","sequence":"additional","affiliation":[{"name":"The Russell H. 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Morgan Department of Radiology and Radiological Science,Johns Hopkins University School of Medicine,Baltimore,MD"},{"name":"The Center for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine,Baltimore,MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tae Hyung","family":"Kim","sequence":"additional","affiliation":[{"name":"The Russell H. Morgan Department of Radiology and Radiological Science,Johns Hopkins University School of Medicine,Baltimore,MD"},{"name":"The Center for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine,Baltimore,MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sung\u2010Mook","family":"Lim","sequence":"additional","affiliation":[{"name":"College of Pharmacy,Sungkyunkwan University,Suwon,Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hana","family":"Eom","sequence":"additional","affiliation":[{"name":"College of Pharmacy,Sungkyunkwan University,Suwon,Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong Gyu","family":"Jo","sequence":"additional","affiliation":[{"name":"College of Pharmacy,Sungkyunkwan University,Suwon,Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Choong\u2010Eun","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Biological Science,Sungkyunkwan University,Suwon,Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raouf","family":"Kechrid","sequence":"additional","affiliation":[{"name":"Laboratory of Liver Diseases,National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health,Bethesda,MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Panagiotis","family":"Mastorakos","sequence":"additional","affiliation":[{"name":"The Center for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine,Baltimore,MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clark","family":"Zhang","sequence":"additional","affiliation":[{"name":"The Center for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine,Baltimore,MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sei Kwang","family":"Hahn","sequence":"additional","affiliation":[{"name":"Department of Materials Science and Engineering,Pohang University of Science and Technology,Pohang,Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ok\u2010Cheol","family":"Jeon","sequence":"additional","affiliation":[{"name":"College of Pharmacy,Seoul National University,Seoul,Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youngro","family":"Byun","sequence":"additional","affiliation":[{"name":"College of Pharmacy,Seoul National University,Seoul,Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kwangmeyung","family":"Kim","sequence":"additional","affiliation":[{"name":"Center for Theragnosis, Korea Institute of Science and Technology,Seoul,Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin","family":"Hanes","sequence":"additional","affiliation":[{"name":"The Center for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine,Baltimore,MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kang Choon","family":"Lee","sequence":"additional","affiliation":[{"name":"College of Pharmacy,Sungkyunkwan University,Suwon,Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin G.","family":"Pomper","sequence":"additional","affiliation":[{"name":"The Russell H. 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