{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T23:42:01Z","timestamp":1793317321363,"version":"4.5.0"},"reference-count":47,"publisher":"American Physiological Society","issue":"1","funder":[{"DOI":"10.13039\/501100000925","name":"Department of Health, Australian Government | National Health and Medical Research Council (NHMRC)","doi-asserted-by":"publisher","award":["1081710"],"award-info":[{"award-number":["1081710"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"Department of Health, Australian Government | National Health and Medical Research Council (NHMRC)","doi-asserted-by":"publisher","award":["1043026"],"award-info":[{"award-number":["1043026"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"Department of Health, Australian Government | National Health and Medical Research Council (NHMRC)","doi-asserted-by":"publisher","award":["1078985"],"award-info":[{"award-number":["1078985"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China (NSFC)","doi-asserted-by":"publisher","award":["81870300"],"award-info":[{"award-number":["81870300"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"published-print":{"date-parts":[[2019,1,1]]},"abstract":"<jats:p>Dilated cardiomyopathy (DCM) is a major cause of heart failure without effective therapy. Fibrogenesis plays a key role in the development of DCM, but little is known of the expression of the profibrotic factor galectin-3 (Gal-3) and its role in DCM pathophysiology. In a mouse DCM model with transgenic (TG) overexpression of mammalian sterile 20-like kinase 1 (Mst1), we studied Gal-3 expression and effects of the Gal-3 inhibitor modified citrus pectin (MCP) or Gal-3 gene knockout (KO). Gal-3 deletion in TG mice (TG\/KO) was achieved by crossbreeding Mst1-TG mice with Gal-3 KO mice. The DCM phenotype was assessed by echocardiography and micromanometry. Cardiac expression of Gal-3 and fibrosis were determined. The cardiac transcriptome was profiled by RNA sequencing. Mst1-TG mice at 3\u22128 mo of age exhibited upregulated expression of Gal-3 by ~40-fold. TG mice had dilatation of cardiac chambers, suppressed left ventricular (LV) ejection fraction, poor LV contractility and relaxation, a threefold increase in LV collagen content, and upregulated fibrotic genes. Four-month treatment with MCP showed no beneficial effects. Gal-3 deletion in Mst1-TG mice attenuated chamber dilatation, organ congestion, and fibrogenesis. RNA sequencing identified profound disturbances by Mst1 overexpression in the cardiac transcriptome, which largely remained in TG\/KO hearts. Gal-3 deletion in Mst1-TG mice, however, partially reversed the dysregulated transcriptional signaling involving extracellular matrix remodeling and collagen formation. We conclude that cardiac Mst1 activation leads to marked Gal-3 upregulation and transcriptome disturbances in the heart. Gal-3 deficiency attenuated cardiac remodeling and fibrotic signaling.<\/jats:p><jats:p>NEW &amp; NOTEWORTHY We found in a transgenic mouse dilated cardiomyopathy (DCM) model a pronounced upregulation of galectin-3 in cardiomyocytes. Galectin-3 gene deletion reduced cardiac fibrosis and fibrotic gene profiles and ameliorated cardiac remodeling and dysfunction. These benefits of galectin-3 deletion were in contrast to the lack of effect of treatment with the galectin-3 inhibitor modified citrus pectin. Our study suggests that suppression of galectin-3 mRNA expression could be used to treat DCM with high cardiac galectin-3 content.<\/jats:p>","DOI":"10.1152\/ajpheart.00609.2018","type":"journal-article","created":{"date-parts":[[2018,11,2]],"date-time":"2018-11-02T15:26:51Z","timestamp":1541172411000},"page":"H45-H60","source":"Crossref","is-referenced-by-count":61,"title":["Galectin-3 deficiency ameliorates fibrosis and remodeling in dilated cardiomyopathy mice with enhanced Mst1 signaling"],"prefix":"10.1152","volume":"316","author":[{"given":"My-Nhan","family":"Nguyen","sequence":"first","affiliation":[{"name":"Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia"},{"name":"Central Clinical School, Monash University, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Ziemann","sequence":"additional","affiliation":[{"name":"Department of Diabetes, Monash University, Melbourne, Victoria, 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