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A micellized bone morphogenetic protein-7 prodrug ameliorates liver fibrosis by suppressing transforming growth factor- β signaling

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dc.contributor.author구민희-
dc.contributor.author김승업-
dc.contributor.author김현실-
dc.contributor.author박준용-
dc.contributor.author안상훈-
dc.contributor.author양재문-
dc.contributor.author육종인-
dc.contributor.author정철희-
dc.date.accessioned2022-05-09T17:11:36Z-
dc.date.available2022-05-09T17:11:36Z-
dc.date.issued2022-02-
dc.identifier.issn2156-6976-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/188430-
dc.description.abstractBone morphogenetic protein-7 (BMP-7) antagonizes transforming growth factor-β (TGF-β), which is critically involved in liver fibrogenesis. Here, we designed a micelle formulation consisting of a protein transduction domain (PTD) fused BMP-7 polypeptide (mPTD-BMP-7) to enhance endocytic delivery, and investigated its ability to ameliorate liver fibrosis. The mPTD-BMP-7 formulation was efficiently delivered into cells via endocytosis, where it inhibited TGF-β mediated epithelial-mesenchymal transition. After successfully demonstrating delivery of fluorescently labeled mPTD-BMP-7 into the murine liver in vivo, we tested the mPTD-BMP-7 formulation in a murine liver fibrosis model, developed by repeated intraperitoneal injection of hepatotoxic carbon tetrachloride, twice weekly from 4 to 16 weeks. mPTD-BMP-7 effects were tested by injecting the mPTD-BMP-7 formulation (or vehicle control) into the lateral tail at a dose of 50 (n=8) or 500 μg/kg (n=10), also twice per week from 4 to 16 weeks. Vehicle-treated control mice developed fibrous septa surrounding the liver parenchyma and marked portal-to-portal bridging with occasional nodules, whereas mice treated with mPTD-BMP-7 showed only fibrous expansion of some portal areas, with or without short fibrous septa. Using the Ishak scoring system, we found that the fibrotic burden was significantly lower in mPTD-BMP-7 treated mice than in control mice (all P<0.001). Treatment with mPTD-BMP-7 protected tight junctions between hepatocytes and reduced extracellular matrix protein levels. It also significantly decreased mRNA levels of collagen 1A, smooth muscle α-actin, and connective tissue growth factor compared with that in control mice (all P<0.001). Collectively, out results indicate that mPTD-BMP-7, a prodrug formulation of BMP-7, ameliorates liver fibrosis by suppressing the TGF-β signaling pathway in a murine liver fibrosis model.-
dc.description.statementOfResponsibilityopen-
dc.formatapplication/pdf-
dc.languageEnglish-
dc.publishere-Century Publishing Corporation-
dc.relation.isPartOfAMERICAN JOURNAL OF CANCER RESEARCH-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.titleA micellized bone morphogenetic protein-7 prodrug ameliorates liver fibrosis by suppressing transforming growth factor- β signaling-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentDept. of Radiology (영상의학교실)-
dc.contributor.googleauthorKyungjoo Cho-
dc.contributor.googleauthorNam Hee Kim-
dc.contributor.googleauthorSang Hyun Seo-
dc.contributor.googleauthorSang Hyun Song-
dc.contributor.googleauthorChul Hee Jeong-
dc.contributor.googleauthorHyun Sil Kim-
dc.contributor.googleauthorJo Eun Um-
dc.contributor.googleauthorMinhee Ku-
dc.contributor.googleauthorJaemoon Yang-
dc.contributor.googleauthorJun Yong Park-
dc.contributor.googleauthorSang Hoon Ahn-
dc.contributor.googleauthorJong In Yook-
dc.contributor.googleauthorSeung Up Kim-
dc.contributor.localIdA00191-
dc.contributor.localIdA00654-
dc.contributor.localIdA01121-
dc.contributor.localIdA01675-
dc.contributor.localIdA02226-
dc.contributor.localIdA02315-
dc.contributor.localIdA02536-
dc.relation.journalcodeJ00070-
dc.identifier.eissn2156-6976-
dc.identifier.pmid35261800-
dc.subject.keywordBone morphogenetic protein-
dc.subject.keywordliver fibrosis-
dc.subject.keywordtrans-activator of transcription-fusion polypeptide-
dc.subject.keywordtransforming growth factor-
dc.contributor.alternativeNameKu, Min Hee-
dc.contributor.affiliatedAuthor구민희-
dc.contributor.affiliatedAuthor김승업-
dc.contributor.affiliatedAuthor김현실-
dc.contributor.affiliatedAuthor박준용-
dc.contributor.affiliatedAuthor안상훈-
dc.contributor.affiliatedAuthor양재문-
dc.contributor.affiliatedAuthor육종인-
dc.citation.volume12-
dc.citation.number2-
dc.citation.startPage763-
dc.citation.endPage778-
dc.identifier.bibliographicCitationAMERICAN JOURNAL OF CANCER RESEARCH, Vol.12(2) : 763-778, 2022-02-
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Radiology (영상의학교실) > 1. Journal Papers
2. College of Dentistry (치과대학) > Dept. of Oral Pathology (구강병리학교실) > 1. Journal Papers

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