{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T18:37:16Z","timestamp":1793471836619,"version":"4.5.0"},"reference-count":54,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2021,11,23]],"date-time":"2021-11-23T00:00:00Z","timestamp":1637625600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2022,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Cardiomyopathy is an irreparable loss and novel strategies are needed to induce resident cardiac progenitor cell (CPC) proliferation in situ to enhance the possibility of cardiac regeneration. Here, we sought to identify the potential roles of glycogen synthase kinase\u20103\u03b2 (GSK\u20103\u03b2), a critical regulator of cell proliferation and differentiation, in CPC proliferation post\u2010myocardial infarction (MI).<\/jats:p>\n                  <jats:p>Cardiomyocyte\u2010specific conditional GSK\u20103\u03b2 knockout (cKO) and littermate control mice were employed and challenged with MI. Though cardiac left ventricular chamber dimension and contractile functions were comparable at 2 weeks post\u2010MI, cKO mice displayed significantly preserved LV chamber and contractile function versus control mice at 4 weeks post\u2010MI. Consistent with protective phenotypes, an increased percentage of c\u2010kit\u2010positive cells (KPCs) were observed in the cKO hearts at 4 and 6 weeks post\u2010MI which was accompanied by increased levels of cardiomyocyte proliferation. Further analysis revealed that the observed increased number of KPCs in the ischemic cKO hearts was mainly from a cardiac lineage, as the majority of identified KPCs were negative for the hematopoietic lineage marker, CD45. Mechanistically, cardiomyocyte\u2010GSK\u20103\u03b2 profoundly suppresses the expression and secretion of growth factors, including basic\u2010fibroblast growth factor, angiopoietin\u20102, erythropoietin, stem cell factor, platelet\u2010derived growth factor\u2010BB, granulocyte colony\u2010stimulating factor, and vascular endothelial growth factor, post\u2010hypoxia.<\/jats:p>\n                  <jats:p>In conclusion, our findings strongly suggest that loss of cardiomyocyte\u2010GSK\u20103\u03b2 promotes cardiomyocyte and resident CPC proliferation post\u2010MI. The induction of cardiomyocyte and CPC proliferation in the ischemic cKO hearts is potentially regulated by autocrine and paracrine signaling governed by dysregulated growth factors post\u2010MI. A strategy to inhibit cardiomyocyte\u2010GSK\u20103\u03b2 could be helpful for the promotion of in situ cardiac regeneration post\u2010ischemic injury.<\/jats:p>","DOI":"10.1002\/jcp.30644","type":"journal-article","created":{"date-parts":[[2021,11,23]],"date-time":"2021-11-23T07:27:21Z","timestamp":1637652441000},"page":"1804-1817","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Cardiomyocyte\u2010GSK\u20103\u03b2 deficiency induces cardiac progenitor cell proliferation in the ischemic heart through paracrine mechanisms"],"prefix":"10.1002","volume":"237","author":[{"given":"Ayesha M.","family":"Yusuf","sequence":"first","affiliation":[{"name":"Department of Basic Medical Sciences, College of Medicine University of Sharjah Sharjah UAE"},{"name":"Cardiovascular Research Group, Sharjah Institute for Medical Research University of Sharjah Sharjah UAE"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8485-7172","authenticated-orcid":false,"given":"Rizwan","family":"Qaisar","sequence":"additional","affiliation":[{"name":"Department of Basic Medical Sciences, College of Medicine University of Sharjah Sharjah UAE"},{"name":"Cardiovascular Research Group, Sharjah Institute for Medical Research University of Sharjah Sharjah UAE"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abaher O.","family":"Al\u2010Tamimi","sequence":"additional","affiliation":[{"name":"Department of Basic Medical Sciences, College of Medicine University of Sharjah Sharjah UAE"},{"name":"Cardiovascular Research Group, Sharjah Institute for Medical Research University of Sharjah Sharjah UAE"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3613-6754","authenticated-orcid":false,"given":"Manju Nidagodu","family":"Jayakumar","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Group, Sharjah Institute for Medical Research University of Sharjah Sharjah UAE"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3731-5797","authenticated-orcid":false,"given":"James R.","family":"Woodgett","sequence":"additional","affiliation":[{"name":"Department of Medical Biophysics, Sinai Health System, Lunenfeld\u2010Tanenbaum Research Institute University of Toronto Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walter J.","family":"Koch","sequence":"additional","affiliation":[{"name":"Center for Translational Medicine, Lewis Katz School of Medicine Temple University Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6530-6068","authenticated-orcid":false,"given":"Firdos","family":"Ahmad","sequence":"additional","affiliation":[{"name":"Department of Basic Medical Sciences, College of Medicine University of Sharjah Sharjah UAE"},{"name":"Cardiovascular Research Group, Sharjah Institute for Medical Research University of Sharjah Sharjah UAE"},{"name":"Center for Translational Medicine, Lewis Katz School of Medicine Temple University Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,11,23]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2014.04.068"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2019.03.020"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2019.165609"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2019.118616"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00032.2006"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.21037\/sci.2017.11.06"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V77.11.2316.2316"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2014.11.016"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms17010063"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1634\/stemcells.2005-0029"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/35096075"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2007.04.001"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-021-02423-5"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R800077200"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.110.223925"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcard.2018.01.013"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.119.045566"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.115.305373"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI25878"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-018-0400-9"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/aps.2014.150"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2011.00040"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI36245"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1203800"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0007443"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature10147"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.116.303613"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.113.008364"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.111.050666"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.117.311059"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.00763-08"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1200708"},{"issue":"3","key":"e_1_2_9_34_1","first-page":"271","article-title":"Cardiac regeneration using growth factors: Advances and challenges","volume":"107","author":"Reboucas J. S.","year":"2016","journal-title":"Arquivos Brasileiros de Cardiologia"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.4252\/wjsc.v9.i1.9"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.15420\/cfr.2016:25:2"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature06800"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvy255"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvu022"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrcardio.2013.94"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.7888\/juoeh.40.147"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1018925108"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000183733.53101.11"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0500169102"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.240500302"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcdb.2019.10.011"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-201X.2002.00989.x"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.109.211482"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200522326"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2019.01049"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2019.06.065"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00187.2013"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1097\/MCA.0b013e32834523f8"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.116.309093"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.116.308544"}],"container-title":["Journal of Cellular Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcp.30644","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jcp.30644","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcp.30644","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,25]],"date-time":"2023-08-25T09:37:44Z","timestamp":1692956264000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jcp.30644"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,23]]},"references-count":54,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2022,3]]}},"alternative-id":["10.1002\/jcp.30644"],"URL":"https:\/\/doi.org\/10.1002\/jcp.30644","archive":["Portico"],"relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2021.08.28.458018","asserted-by":"object"}]},"ISSN":["0021-9541","1097-4652"],"issn-type":[{"value":"0021-9541","type":"print"},{"value":"1097-4652","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,23]]},"assertion":[{"value":"2021-09-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-11-09","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-11-23","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}