{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T23:21:43Z","timestamp":1792797703628,"version":"4.5.0"},"reference-count":73,"publisher":"American Society for Clinical Investigation","issue":"15","license":[{"start":{"date-parts":[[2019,8,8]],"date-time":"2019-08-08T00:00:00Z","timestamp":1565222400000},"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":["R01 HL142217,R01AR071301"],"award-info":[{"award-number":["R01 HL142217,R01AR071301"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,8,8]]},"abstract":"<jats:p>\n                    Collagen production in the adult heart is thought to be regulated by the fibroblast, although cardiomyocytes and endothelial cells also express multiple collagen mRNAs. Molecular chaperones are required for procollagen biosynthesis, including heat shock protein 47 (Hsp47). To determine the cell types critically involved in cardiac injury\u2013induced fibrosis the\n                    <jats:italic>Hsp47<\/jats:italic>\n                    gene was deleted in cardiomyocytes, endothelial cells, or myofibroblasts. Deletion of\n                    <jats:italic>Hsp47<\/jats:italic>\n                    from cardiomyocytes during embryonic development or adult stages, or deletion from adult endothelial cells, did not affect cardiac fibrosis after pressure overload injury. However, myofibroblast-specific ablation of\n                    <jats:italic>Hsp47<\/jats:italic>\n                    blocked fibrosis and deposition of collagens type I, III, and V following pressure overload as well as significantly reduced cardiac hypertrophy. Fibroblast-specific\n                    <jats:italic>Hsp47<\/jats:italic>\n                    -deleted mice showed lethality after myocardial infarction injury, with ineffective scar formation and ventricular wall rupture. Similarly, only myofibroblast-specific deletion of\n                    <jats:italic>Hsp47<\/jats:italic>\n                    reduced fibrosis and disease in skeletal muscle in a mouse model of muscular dystrophy. Mechanistically, deletion of\n                    <jats:italic>Hsp47<\/jats:italic>\n                    from myofibroblasts reduced mRNA expression of fibrillar collagens and attenuated their proliferation in the heart without affecting paracrine secretory activity of these cells. The results show that myofibroblasts are the primary mediators of tissue fibrosis and scar formation in the injured adult heart, which unexpectedly affects cardiomyocyte hypertrophy.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.128722","type":"journal-article","created":{"date-parts":[[2019,7,2]],"date-time":"2019-07-02T12:00:55Z","timestamp":1562068855000},"source":"Crossref","is-referenced-by-count":99,"title":["Cell-specific ablation of Hsp47 defines the collagen-producing cells in the injured heart"],"prefix":"10.1172","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3860-5331","authenticated-orcid":true,"given":"Hadi","family":"Khalil","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Cincinnati Children\u2019s Hospital Medical Center, 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