{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T00:51:01Z","timestamp":1792111861258,"version":"4.4.0"},"reference-count":69,"publisher":"American Society for Clinical Investigation","issue":"9","license":[{"start":{"date-parts":[[2025,5,1]],"date-time":"2025-05-01T00:00:00Z","timestamp":1746057600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["K22NS104135"],"award-info":[{"award-number":["K22NS104135"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["AR055295"],"award-info":[{"award-number":["AR055295"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000052","name":"NIH Office of the Director","doi-asserted-by":"crossref","award":["S10OD023461"],"award-info":[{"award-number":["S10OD023461"]}],"id":[{"id":"10.13039\/100000052","id-type":"DOI","asserted-by":"crossref"}]},{"name":"University of Pennsylvania Orphan Disease Center","award":["MDBR"],"award-info":[{"award-number":["MDBR"]}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["ZIA NS003129"],"award-info":[{"award-number":["ZIA NS003129"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,5,1]]},"abstract":"<jats:p>\n                    Collagen VI\u2013related disorders (\n                    <jats:italic>COL6<\/jats:italic>\n                    -RDs) are a group of rare muscular dystrophies caused by pathogenic variants in collagen VI genes (\n                    <jats:italic>COL6A1<\/jats:italic>\n                    ,\n                    <jats:italic>COL6A2<\/jats:italic>\n                    , and\n                    <jats:italic>COL6A3<\/jats:italic>\n                    ). Collagen type VI is a heterotrimeric, microfibrillar component of the muscle extracellular matrix (ECM), predominantly secreted by resident fibroadipogenic precursor cells in skeletal muscle. The absence or mislocalization of collagen VI in the ECM underlies the noncell-autonomous dysfunction and dystrophic changes in skeletal muscle with a yet elusive direct mechanistic link between the ECM and myofiber dysfunction. Here, we conducted a comprehensive natural history and outcome study in a mouse model of\n                    <jats:italic>COL6<\/jats:italic>\n                    -RDs (\n                    <jats:italic>\n                      Col6a2\n                      <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    mice) using standardized (TREAT-NMD) functional, histological, and physiological parameters. Notably, we identify a conspicuous dysregulation of the TGF-\u03b2 pathway early in the disease process and propose that the collagen VI\u2013deficient matrix is not capable of regulating the dynamic TGF-\u03b2 bioavailability both at baseline and in response to muscle injury. Thus, we propose a new mechanism for pathogenesis of the disease that links the ECM regulation of TGF-\u03b2 with downstream skeletal muscle abnormalities, paving the way for the development and validation of therapeutics that target this pathway.\n                  <\/jats:p>","DOI":"10.1172\/jci173354","type":"journal-article","created":{"date-parts":[[2025,5,1]],"date-time":"2025-05-01T07:59:44Z","timestamp":1746086384000},"source":"Crossref","is-referenced-by-count":18,"title":["Collagen type VI regulates TGF-\u03b2 bioavailability in skeletal muscle in mice"],"prefix":"10.1172","volume":"135","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5313-9514","authenticated-orcid":true,"given":"Payam","family":"Mohassel","sequence":"first","affiliation":[{"name":"National Institute of Neurological Disorders and Stroke, Neuromuscular and Neurogenetic Disorders of Childhood Section, NIH, Bethesda, Maryland, USA."},{"name":"Department of Neurology, Johns Hopkins University School of 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Section, Intramural Information Technology & Bioinformatics Program, National Institute of Neurological Disorders and Stroke, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gina","family":"Norato","sequence":"additional","affiliation":[{"name":"Clinical Trials Unit, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew A.","family":"Nalls","sequence":"additional","affiliation":[{"name":"National Institute of Neurological Disorders and Stroke, Neuromuscular and Neurogenetic Disorders of Childhood Section, NIH, Bethesda, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7304-7411","authenticated-orcid":true,"given":"Pomi","family":"Yun","sequence":"additional","affiliation":[{"name":"National Institute of Neurological Disorders and Stroke, Neuromuscular and Neurogenetic Disorders of Childhood Section, NIH, Bethesda, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tracy","family":"Ogata","sequence":"additional","affiliation":[{"name":"National Institute of Neurological Disorders and Stroke, Neuromuscular and Neurogenetic Disorders of Childhood Section, NIH, Bethesda, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Silverstein","sequence":"additional","affiliation":[{"name":"National Institute of Neurological Disorders and Stroke, Neuromuscular and Neurogenetic Disorders of Childhood Section, NIH, Bethesda, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Sleboda","sequence":"additional","affiliation":[{"name":"Department of Ecology and Evolutionary Biology, University of California, Irvine, Irvine, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas 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