{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T02:22:01Z","timestamp":1760235721522,"version":"build-2065373602"},"reference-count":73,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2021,9,18]],"date-time":"2021-09-18T00:00:00Z","timestamp":1631923200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Muscular dystrophy is a progressively worsening and lethal disease, where accumulation of functionality-impairing fibrosis plays a key pathogenic role. Transforming growth factor-\u03b21 (TGF\u03b21) is a central signaling molecule in the development of fibrosis in muscular dystrophic humans and mice. Inhibition of TGF\u03b21 has proven beneficial in mouse models of muscular dystrophy, but the global strategies of TGF\u03b21 inhibition produce significant detrimental side effects. Here, we investigated whether murine muscular dystrophy lesion-specific inhibition of TGF\u03b21 signaling by the targeted delivery of therapeutic decorin (a natural TGF\u03b2 inhibitor) by a vascular homing peptide CAR (CARSKNKDC) would reduce skeletal muscle fibrosis and pathology and increase functional characteristics of skeletal muscle. We demonstrate that CAR peptide homes to dystrophic lesions with specificity in two muscular dystrophy models. Recombinant fusion protein consisting of CAR peptide and decorin homes selectively to sites of skeletal muscle damage in mdxDBA2\/J and gamma-sarcoglycan deficient DBA2\/J mice. This targeted delivery reduced TGF\u03b21 signaling as demonstrated by reduced nuclear pSMAD staining. Three weeks of targeted decorin treatment decreased both membrane permeability and fibrosis and improved skeletal muscle function in comparison to control treatments in the mdxD2 mice. These results show that selective delivery of decorin to the sites of skeletal muscle damage attenuates the progression of murine muscular dystrophy.<\/jats:p>","DOI":"10.3390\/pharmaceutics13091506","type":"journal-article","created":{"date-parts":[[2021,9,21]],"date-time":"2021-09-21T22:34:01Z","timestamp":1632263641000},"page":"1506","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Systemically Administered Homing Peptide Targets Dystrophic Lesions and Delivers Transforming Growth Factor-\u03b2 (TGF\u03b2) Inhibitor to Attenuate Murine Muscular Dystrophy Pathology"],"prefix":"10.3390","volume":"13","author":[{"given":"Aqsa","family":"Iqbal","sequence":"first","affiliation":[{"name":"Department of Physiology and Biophysics, University of Illinois at Chicago, Chicago, IL 60612, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ulrike","family":"May","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Health Technology, Tampere University, 33014 Tampere, Finland"},{"name":"Department of Orthopedics & Traumatology, Tampere University Hospital, 33520 Tampere, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stuart N.","family":"Prince","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Health Technology, Tampere University, 33014 Tampere, Finland"},{"name":"Department of Orthopedics & Traumatology, Tampere University Hospital, 33520 Tampere, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4027-1759","authenticated-orcid":false,"given":"Tero A.H.","family":"J\u00e4rvinen","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Health Technology, Tampere University, 33014 Tampere, Finland"},{"name":"Department of Orthopedics & Traumatology, Tampere University Hospital, 33520 Tampere, Finland"},{"name":"Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2626-3787","authenticated-orcid":false,"given":"Ahlke","family":"Heydemann","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics, University of Illinois at Chicago, Chicago, IL 60612, USA"},{"name":"Center for Cardiovascular Research, University of Illinois at Chicago, Chicago, IL 60612, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1016\/S0140-6736(02)07815-7","article-title":"The muscular dystrophies","volume":"359","author":"Emery","year":"2002","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1186\/2044-5040-1-21","article-title":"Aberrant repair and fibrosis development in skeletal muscle","volume":"1","author":"Mann","year":"2011","journal-title":"Skelet. 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