{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T18:08:01Z","timestamp":1781719681388,"version":"3.54.5"},"reference-count":32,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2020,11,19]],"date-time":"2020-11-19T00:00:00Z","timestamp":1605744000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>Tubulointerstitial renal fibrosis is a chronic disease process affecting chronic kidney disease (CKD). While the etiological role of transforming growth factor-beta (TGF-\u03b2) is well known for epithelial\u2013mesenchymal transition (EMT) in chronic kidney disease, effective therapeutics for renal fibrosis are largely limited. As a member of the TGF-\u03b2 superfamily, bone morphogenetic protein-7 (BMP-7) plays an important role as an endogenous antagonist of TGF-\u03b2, 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<jats:italic>in vivo<\/jats:italic>. 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-\u03b2\u2013mediated epithelial\u2013mesenchymal transition process<jats:italic>in vitro<\/jats:italic>and in an<jats:italic>in vivo<\/jats:italic>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\u2019s space and inhibits unilateral ureter obstruction\u2013induced renal fibrosis in pigs. Our results provide a novel therapeutic targeting TGF-\u03b2\u2013mediated renal fibrosis and other organs as well as a clinically available approach for kidney.<\/jats:p>","DOI":"10.3389\/fphar.2020.591275","type":"journal-article","created":{"date-parts":[[2020,11,19]],"date-time":"2020-11-19T13:11:26Z","timestamp":1605791486000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":25,"title":["Micellized Protein Transduction Domain-Bone Morphogenetic Protein-7 Efficiently Blocks Renal Fibrosis Via Inhibition of Transforming Growth Factor-Beta\u2013Mediated Epithelial\u2013Mesenchymal Transition"],"prefix":"10.3389","volume":"11","author":[{"given":"Seonghun","family":"Kim","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheol-Hee","family":"Jeong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang Hyun","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jo Eun","family":"Um","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyun Sil","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun Seop","family":"Yun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dawool","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eunae Sandra","family":"Cho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo Young","family":"Nam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jong In","family":"Yook","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minhee","family":"Ku","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaemoon","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Man-Deuk","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nam Hee","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tae-Hyun","family":"Yoo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2020,11,19]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1159\/000489897","article-title":"Disparities in chronic kidney disease prevalence among males and females in 195 countries: analysis of the global burden of disease 2016 study","volume":"139","author":"Bikbov","year":"2018","journal-title":"Nephron"},{"key":"B2","doi-asserted-by":"publisher","first-page":"490","DOI":"10.1016\/j.cell.2019.12.030","article-title":"Cryo-EM reveals integrin-mediated TGF-\u03b2 activation without release from latent TGF-\u03b2","volume":"180","author":"Campbell","year":"2020","journal-title":"Cell"},{"key":"B3","doi-asserted-by":"publisher","first-page":"668","DOI":"10.1016\/j.yjmcc.2012.08.010","article-title":"A translational study of urine miRNAs in acute myocardial infarction","volume":"53","author":"Cheng","year":"2012","journal-title":"J. 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