{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T04:20:57Z","timestamp":1781151657269,"version":"3.54.1"},"reference-count":59,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2024,6,1]],"date-time":"2024-06-01T00:00:00Z","timestamp":1717200000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100011724","name":"Muscular Dystrophy UK","doi-asserted-by":"publisher","award":["17GRO-PS48-0092-7"],"award-info":[{"award-number":["17GRO-PS48-0092-7"]}],"id":[{"id":"10.13039\/100011724","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Periostin, a multifunctional 90 kDa protein, plays a pivotal role in the pathogenesis of fibrosis across various tissues, including skeletal muscle. It operates within the transforming growth factor beta 1 (Tgf-\u03b21) signalling pathway and is upregulated in fibrotic tissue. Alternative splicing of Periostin\u2019s C-terminal region leads to six protein-coding isoforms. This study aimed to elucidate the contribution of the isoforms containing the amino acids encoded by exon 17 (e17+ Periostin) to skeletal muscle fibrosis and investigate the therapeutic potential of manipulating exon 17 splicing. We identified distinct structural differences between e17+ Periostin isoforms, affecting their interaction with key fibrotic proteins, including Tgf-\u03b21 and integrin alpha V. In vitro mouse fibroblast experimentation confirmed the TGF-\u03b21-induced upregulation of e17+ Periostin mRNA, mitigated by an antisense approach that induces the skipping of exon 17 of the Postn gene. Subsequent in vivo studies in the D2.mdx mouse model of Duchenne muscular dystrophy (DMD) demonstrated that our antisense treatment effectively reduced e17+ Periostin mRNA expression, which coincided with reduced full-length Periostin protein expression and collagen accumulation. The grip strength of the treated mice was rescued to the wild-type level. These results suggest a pivotal role of e17+ Periostin isoforms in the fibrotic pathology of skeletal muscle and highlight the potential of targeted exon skipping strategies as a promising therapeutic approach for mitigating fibrosis-associated complications.<\/jats:p>","DOI":"10.3390\/ijms25116113","type":"journal-article","created":{"date-parts":[[2024,6,3]],"date-time":"2024-06-03T08:19:42Z","timestamp":1717402782000},"page":"6113","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Targeted Antisense Oligonucleotide-Mediated Skipping of Murine Postn Exon 17 Partially Addresses Fibrosis in D2.mdx Mice"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-3520-3200","authenticated-orcid":false,"given":"Jessica","family":"Trundle","sequence":"first","affiliation":[{"name":"Department of Biological Sciences, School of Life Sciences and Environment, Royal Holloway University of London, Surrey TW20 0EX, UK"},{"name":"Developmental Biology and Cancer Research and Teaching Department, University College London Great Ormond Street Institute of Child Health, London WC1N 1EH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7241-9607","authenticated-orcid":false,"given":"Ngoc","family":"Lu-Nguyen","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, School of Life Sciences and Environment, Royal Holloway University of London, Surrey TW20 0EX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0536-5231","authenticated-orcid":false,"given":"Alberto","family":"Malerba","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, School of Life Sciences and Environment, Royal Holloway University of London, Surrey TW20 0EX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda","family":"Popplewell","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, School of Life Sciences and Environment, Royal Holloway University of London, Surrey TW20 0EX, UK"},{"name":"National Horizons Centre, Teesside University, Darlington DL1 1HG, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1016\/0092-8674(87)90579-4","article-title":"Dystrophin: The protein product of the Duchenne muscular dystrophy locus","volume":"51","author":"Hoffman","year":"1987","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1016\/j.nmd.2014.03.008","article-title":"A systematic review and meta-analysis on the epidemiology of Duchenne and Becker muscular dystrophy","volume":"24","author":"Mah","year":"2014","journal-title":"Neuromuscul. 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