{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,14]],"date-time":"2026-11-14T09:13:32Z","timestamp":1794647612285,"version":"4.9.1"},"reference-count":36,"publisher":"Oxford University Press (OUP)","issue":"45","license":[{"start":{"date-parts":[[2022,10,6]],"date-time":"2022-10-06T00:00:00Z","timestamp":1665014400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"crossref","award":["MOP136862 and PJT162422 to MPC, FRN216927 to RAB and PJT37522 to ZK"],"award-info":[{"award-number":["MOP136862 and PJT162422 to MPC, FRN216927 to RAB and PJT37522 to ZK"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100008794","name":"Research Manitoba","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100008794","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Aims<\/jats:title>\n                  <jats:p>In response to pro-fibrotic signals, scleraxis regulates cardiac fibroblast activation in vitro via transcriptional control of key fibrosis genes such as collagen and fibronectin; however, its role in vivo is unknown. The present study assessed the impact of scleraxis loss on fibroblast activation, cardiac fibrosis, and dysfunction in pressure overload-induced heart failure.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and results<\/jats:title>\n                  <jats:p>Scleraxis expression was upregulated in the hearts of non-ischemic dilated cardiomyopathy patients, and in mice subjected to pressure overload by transverse aortic constriction (TAC). Tamoxifen-inducible fibroblast-specific scleraxis knockout (Scx-fKO) completely attenuated cardiac fibrosis, and significantly improved cardiac systolic function and ventricular remodelling, following TAC compared to Scx+\/+ TAC mice, concomitant with attenuation of fibroblast activation. Scleraxis deletion, after the establishment of cardiac fibrosis, attenuated the further functional decline observed in Scx+\/+ mice, with a reduction in cardiac myofibroblasts. Notably, scleraxis knockout reduced pressure overload-induced mortality from 33% to zero, without affecting the degree of cardiac hypertrophy. Scleraxis directly regulated transcription of the myofibroblast marker periostin, and cardiac fibroblasts lacking scleraxis failed to upregulate periostin synthesis and secretion in response to pro-fibrotic transforming growth factor \u03b2.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Scleraxis governs fibroblast activation in pressure overload-induced heart failure, and scleraxis knockout attenuated fibrosis and improved cardiac function and survival. These findings identify scleraxis as a viable target for the development of novel anti-fibrotic treatments.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/eurheartj\/ehac362","type":"journal-article","created":{"date-parts":[[2022,10,6]],"date-time":"2022-10-06T13:02:30Z","timestamp":1665061350000},"page":"4739-4750","source":"Crossref","is-referenced-by-count":49,"title":["Scleraxis and fibrosis in the pressure-overloaded heart"],"prefix":"10.1093","volume":"43","author":[{"given":"Raghu S","family":"Nagalingam","sequence":"first","affiliation":[{"name":"Department of Physiology and Pathophysiology, Rady Faculty of Health Sciences, University of Manitoba , Winnipeg , Canada"},{"name":"Institute of Cardiovascular Sciences, St Boniface Hospital Albrechtsen Research Centre , Winnipeg , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sikta","family":"Chattopadhyaya","sequence":"additional","affiliation":[{"name":"Department of Physiology and 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