Cited 0 times in
A micellized bone morphogenetic protein-7 prodrug ameliorates liver fibrosis by suppressing transforming growth factor- β signaling
DC Field | Value | Language |
---|---|---|
dc.contributor.author | 구민희 | - |
dc.contributor.author | 김승업 | - |
dc.contributor.author | 김현실 | - |
dc.contributor.author | 박준용 | - |
dc.contributor.author | 안상훈 | - |
dc.contributor.author | 양재문 | - |
dc.contributor.author | 육종인 | - |
dc.contributor.author | 정철희 | - |
dc.contributor.author | 김남희 | - |
dc.date.accessioned | 2022-05-09T17:11:36Z | - |
dc.date.available | 2022-05-09T17:11:36Z | - |
dc.date.issued | 2022-02 | - |
dc.identifier.issn | 2156-6976 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/188430 | - |
dc.description.abstract | Bone 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.statementOfResponsibility | open | - |
dc.format | application/pdf | - |
dc.language | English | - |
dc.publisher | e-Century Publishing Corporation | - |
dc.relation.isPartOf | AMERICAN JOURNAL OF CANCER RESEARCH | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.title | A micellized bone morphogenetic protein-7 prodrug ameliorates liver fibrosis by suppressing transforming growth factor- β signaling | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | Dept. of Radiology (영상의학교실) | - |
dc.contributor.googleauthor | Kyungjoo Cho | - |
dc.contributor.googleauthor | Nam Hee Kim | - |
dc.contributor.googleauthor | Sang Hyun Seo | - |
dc.contributor.googleauthor | Sang Hyun Song | - |
dc.contributor.googleauthor | Chul Hee Jeong | - |
dc.contributor.googleauthor | Hyun Sil Kim | - |
dc.contributor.googleauthor | Jo Eun Um | - |
dc.contributor.googleauthor | Minhee Ku | - |
dc.contributor.googleauthor | Jaemoon Yang | - |
dc.contributor.googleauthor | Jun Yong Park | - |
dc.contributor.googleauthor | Sang Hoon Ahn | - |
dc.contributor.googleauthor | Jong In Yook | - |
dc.contributor.googleauthor | Seung Up Kim | - |
dc.contributor.localId | A00191 | - |
dc.contributor.localId | A00654 | - |
dc.contributor.localId | A01121 | - |
dc.contributor.localId | A01675 | - |
dc.contributor.localId | A02226 | - |
dc.contributor.localId | A02315 | - |
dc.contributor.localId | A02536 | - |
dc.relation.journalcode | J00070 | - |
dc.identifier.eissn | 2156-6976 | - |
dc.identifier.pmid | 35261800 | - |
dc.subject.keyword | Bone morphogenetic protein | - |
dc.subject.keyword | liver fibrosis | - |
dc.subject.keyword | trans-activator of transcription-fusion polypeptide | - |
dc.subject.keyword | transforming growth factor | - |
dc.contributor.alternativeName | Ku, Min Hee | - |
dc.contributor.affiliatedAuthor | 구민희 | - |
dc.contributor.affiliatedAuthor | 김승업 | - |
dc.contributor.affiliatedAuthor | 김현실 | - |
dc.contributor.affiliatedAuthor | 박준용 | - |
dc.contributor.affiliatedAuthor | 안상훈 | - |
dc.contributor.affiliatedAuthor | 양재문 | - |
dc.contributor.affiliatedAuthor | 육종인 | - |
dc.citation.volume | 12 | - |
dc.citation.number | 2 | - |
dc.citation.startPage | 763 | - |
dc.citation.endPage | 778 | - |
dc.identifier.bibliographicCitation | AMERICAN JOURNAL OF CANCER RESEARCH, Vol.12(2) : 763-778, 2022-02 | - |
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.