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Micellized Protein Transduction Domain-Bone Morphogenetic Protein-7 Efficiently Blocks Renal Fibrosis Via Inhibition of Transforming Growth Factor-Beta–Mediated Epithelial–Mesenchymal Transition

DC Field Value Language
dc.contributor.author구민희-
dc.contributor.author김남희-
dc.contributor.author김만득-
dc.contributor.author김현실-
dc.contributor.author양재문-
dc.contributor.author유태현-
dc.contributor.author육종인-
dc.contributor.author조은애산드라-
dc.contributor.author정철희-
dc.date.accessioned2020-12-11T08:06:28Z-
dc.date.available2020-12-11T08:06:28Z-
dc.date.issued2020-11-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/180775-
dc.description.abstractTubulointerstitial renal fibrosis is a chronic disease process affecting chronic kidney disease (CKD). While the etiological role of transforming growth factor-beta (TGF-β) is well known for epithelial–mesenchymal transition (EMT) in chronic kidney disease, effective therapeutics for renal fibrosis are largely limited. As a member of the TGF-β superfamily, bone morphogenetic protein-7 (BMP-7) plays an important role as an endogenous antagonist of TGF-β, inhibiting fibrotic progression in many organs. However, soluble rhBMP-7 is hardly available for therapeutics due to its limited pharmacodynamic profile and rapid clearance in clinical settings. In this study, we have developed a novel therapeutic approach with protein transduction domain (PTD) fused BMP-7 in micelle (mPTD-BMP-7) for long-range signaling in vivo. Contrary to rhBMP-7 targeting its cognate receptors, the nano-sized mPTD-BMP-7 is transduced into cells through an endosomal pathway and secreted to the exosome having active BMP-7. Further, transduced mPTD-BMP-7 successfully activates SMAD1/5/8 and inhibits the TGF-β–mediated epithelial–mesenchymal transition process in vitro and in an in vivo unilateral ureter obstruction model. To determine the clinical relevance of our strategy, we also developed an intra-arterial administration of mPTD-BMP-7 through renal artery in pigs. Interestingly, mPTD-BMP-7 through renal artery intervention effectively delivered into Bowman’s space and inhibits unilateral ureter obstruction–induced renal fibrosis in pigs. Our results provide a novel therapeutic targeting TGF-β–mediated renal fibrosis and other organs as well as a clinically available approach for kidney.-
dc.description.statementOfResponsibilityopen-
dc.formatapplication/pdf-
dc.languageEnglish-
dc.publisherFrontiers Media-
dc.relation.isPartOfFRONTIERS IN PHARMACOLOGY-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.titleMicellized Protein Transduction Domain-Bone Morphogenetic Protein-7 Efficiently Blocks Renal Fibrosis Via Inhibition of Transforming Growth Factor-Beta–Mediated Epithelial–Mesenchymal Transition-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentDept. of Radiology (영상의학교실)-
dc.contributor.googleauthorSeonghun Kim-
dc.contributor.googleauthorCheol-Hee Jeong-
dc.contributor.googleauthorSang Hyun Song-
dc.contributor.googleauthorJo Eun Um-
dc.contributor.googleauthorHyun Sil Kim-
dc.contributor.googleauthorJun Seop Yun-
dc.contributor.googleauthorDawool Han-
dc.contributor.googleauthorEunae Sandra Cho-
dc.contributor.googleauthorBo Young Nam-
dc.contributor.googleauthorJong In Yook-
dc.contributor.googleauthorMinhee Ku-
dc.contributor.googleauthorJaemoon Yang-
dc.contributor.googleauthorMan-Deuk Kim-
dc.contributor.googleauthorNam Hee Kim-
dc.contributor.googleauthorTae-Hyun Yoo-
dc.identifier.doi10.3389/fphar.2020.591275-
dc.contributor.localIdA00191-
dc.contributor.localIdA00360-
dc.contributor.localIdA00420-
dc.contributor.localIdA01121-
dc.contributor.localIdA02315-
dc.contributor.localIdA02526-
dc.contributor.localIdA02536-
dc.contributor.localIdA04799-
dc.relation.journalcodeJ03340-
dc.identifier.eissn1663-9812-
dc.contributor.alternativeNameKu, Min Hee-
dc.contributor.affiliatedAuthor구민희-
dc.contributor.affiliatedAuthor김남희-
dc.contributor.affiliatedAuthor김만득-
dc.contributor.affiliatedAuthor김현실-
dc.contributor.affiliatedAuthor양재문-
dc.contributor.affiliatedAuthor유태현-
dc.contributor.affiliatedAuthor육종인-
dc.contributor.affiliatedAuthor조은애산드라-
dc.citation.volume11-
dc.citation.startPage591275-
dc.identifier.bibliographicCitationFRONTIERS IN PHARMACOLOGY, Vol.11 : 591275, 2020-11-
Appears in Collections:
2. College of Dentistry (치과대학) > Research Institute (부설연구소) > 1. Journal Papers
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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