{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T13:01:05Z","timestamp":1790773265994,"version":"4.1.0"},"reference-count":106,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T00:00:00Z","timestamp":1787961600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T00:00:00Z","timestamp":1787961600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"publisher","award":["PG\/22\/11172"],"award-info":[{"award-number":["PG\/22\/11172"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000288","name":"Royal Society","doi-asserted-by":"publisher","award":["RSG\/R1\/180198"],"award-info":[{"award-number":["RSG\/R1\/180198"]}],"id":[{"id":"10.13039\/501100000288","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Extracellular Vesicle"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Pharmacological tools to selectively modulate extracellular vesicle (EV) secretion are scarce. Here, we identify the ALK5 (TGF\u2010\u03b2 receptor I) inhibitor SD\u2010208 as a potent suppressor of small EV (sEV) secretion that acts independently of its canonical anti\u2010fibrotic activity. SD\u2010208 not only reversed myofibroblast activation but also markedly inhibited sEV secretion. Strikingly, this inhibitory effect persisted in non\u2010activated cardiac fibroblasts and non\u2010fibrotic HEK293 cells, demonstrating that SD\u2010208 regulates EV secretion through mechanisms uncoupled from TGF\u2010\u03b2\/Smad signalling. Mechanistic analyses revealed that SD\u2010208 disrupts vesicle trafficking rather than EV biogenesis. Reduced secretion of CD63\n                    <jats:sup>+<\/jats:sup>\n                    EVs was accompanied by intracellular accumulation of CD63\n                    <jats:sup>+<\/jats:sup>\n                    structures and their selective diversion into LAMP1\n                    <jats:sup>+<\/jats:sup>\n                    lysosomes. Proteomic profiling of SD\u2010208\u2010treated and control HEK293 cells and cardiac fibroblasts revealed dysregulation of vesicle trafficking pathways, enrichment of ubiquitin ligase complexes, and enhanced endosome\u2010to\u2010lysosome transport. Together, these findings demonstrate that SD\u2010208 diverts CD63\n                    <jats:sup>+<\/jats:sup>\n                    multivesicular bodies (MVBs) from a secretory fate toward lysosomal degradation. This work identifies SD\u2010208 as a small\u2010molecule tool to interrogate the secretory\u2010versus\u2010degradative fate of MVBs and uncovers a new regulatory link between lysosomal pathways and EV trafficking. Beyond its established role as an anti\u2010fibrotic agent, SD\u2010208 provides mechanistic and therapeutic opportunities for the control of EV secretion in diseases such as fibrosis, cardiac remodelling, hypertrophic cardiomyopathy, and cancer.\n                  <\/jats:p>","DOI":"10.1002\/jev2.70362","type":"journal-article","created":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T18:32:01Z","timestamp":1788028321000},"source":"Crossref","is-referenced-by-count":0,"title":["Pharmacological Inhibition of Small Extracellular Vesicle Secretion by ALK5i SD\u2010208 via Lysosomal Rerouting of CD63+ Compartments"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0282-6768","authenticated-orcid":false,"given":"Rahul","family":"Sanwlani","sequence":"first","affiliation":[{"name":"School of Biosciences University of Surrey  Guildford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgina 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