{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T14:44:58Z","timestamp":1776350698445,"version":"3.51.2"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2015,10,10]],"date-time":"2015-10-10T00:00:00Z","timestamp":1444435200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100004663","name":"Taiwan Ministry of Science and Technology","doi-asserted-by":"crossref","award":["MOST 102-2320-B-002-039"],"award-info":[{"award-number":["MOST 102-2320-B-002-039"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004663","name":"Taiwan Ministry of Science and Technology","doi-asserted-by":"crossref","award":["MOST 103-2320-B002-032-MY2"],"award-info":[{"award-number":["MOST 103-2320-B002-032-MY2"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Heart failure due to myocardial infarction (MI) is a major cause of morbidity and mortality in the world. We found previously that A83-01, a TGF\u03b2RI inhibitor, could facilitate cardiac repair in post-MI mice and induce the expansion of a Nkx2.5\u2009+\u2009cardiomyoblast population. This study aimed to investigate the key autocrine\/paracrine factors regulated by A83-01 in the injured heart and the mechanism of cardioprotection by this molecule. Using a previously described transgenic Nkx2.5 enhancer-green fluorescent protein (GFP) reporter mice, we isolated cardiac progenitor cells (CPC) including Nkx2.5-GFP\u2009+\u2009(Nkx2.5+), sca1+, and Nkx2.5+\/sca1\u2009+\u2009cells. A83-01 was found to induce proliferation of these three subpopulations mainly through increasing Birc5 expression in the MEK\/ERK-dependent pathway. Survivin, encoded by Birc5, could also directly proliferate Nkx2.5\u2009+\u2009cells and enhance cultured cardiomyocytes viability. A83-01 could also reverse the downregulation of Birc5 in postinjured mice hearts (n\u2009=\u20096) to expand CPCs. Moreover, the increased Wnt3a in postinjured hearts could decrease CPCs, which could be reversed by A83-01 via inhibiting Fzd6 and Wnt1-induced signaling protein 1 expressions in CPCs. Next, we used inducible \u03b1MHC-cre\/mTmG mice to label cardiomyocytes with GFP and nonmyocytes with RFP. We found A83-01 preserved more GFP\u2009+\u2009myocytes (68.6%\u2009\u00b1\u20093.1% vs. 80.9%\u2009\u00b1\u20093.0%; p\u2009&amp;lt;\u2009.05, n\u2009=\u20096) and fewer renewed RFP\u2009+\u2009myocytes (0.026%\u2009\u00b1\u20090.005% vs. 0.062%\u2009\u00b1\u20090.008%; p\u2009&amp;lt;\u2009.05, n\u2009=\u20096) in parallel with less cardiac fibrosis in isoprenaline-injected mice treated with A83-01. TGF\u03b2RI inhibition in an injured adult heart could both stimulate the autocrine\/paracrine activity of survivin and inhibit Wnt in CPCs to mediate cardioprotection and improve cardiac function.<\/jats:p>","DOI":"10.1002\/stem.2216","type":"journal-article","created":{"date-parts":[[2015,9,29]],"date-time":"2015-09-29T16:23:39Z","timestamp":1443543819000},"page":"445-455","source":"Crossref","is-referenced-by-count":17,"title":["Cardioprotective Actions of TGF\u03b2RI Inhibition Through Stimulating Autocrine\/Paracrine of Survivin and Inhibiting Wnt in Cardiac Progenitors"],"prefix":"10.1093","volume":"34","author":[{"given":"Yu-Sian","family":"Ho","sequence":"first","affiliation":[{"name":"Institute of Pharmacology, College of Medicine, National Taiwan University, Taipei City, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wan-Hsuan","family":"Tsai","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology, College of Medicine, National Taiwan University, Taipei City, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fen-Chiung","family":"Lin","sequence":"additional","affiliation":[{"name":"Graduate Institute of Clinical Medicine, Taipei Medical University, Taipei City, Taiwan"},{"name":"Division of Cardiology, Linkou Chang Gung Memorial Hospital, Taoyuan City, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei-Pang","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Life Science, National Taiwan University, Taipei City, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lung-Chun","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei City, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sean M.","family":"Wu","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Department of Medicine, Cardiovascular Institute, Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu-Ru","family":"Liu","sequence":"additional","affiliation":[{"name":"Laboratory Animal Center, College of Medicine, National Taiwan University, Taipei City, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wen-Pin","family":"Chen","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology, College of Medicine, National Taiwan University, Taipei City, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2015,10,10]]},"reference":[{"key":"2022010603590040200_stem2216-bib-0001","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1161\/CIRCRESAHA.112.274662","article-title":"Sca-1 knockout impairs myocardial and cardiac progenitor cell 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