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Thus, it is important to understand the underlying molecular mechanisms that modulate this system. Here, we show that FGFR\u20101 can interact with the TNF receptor superfamily member fibroblast growth factor\u2010inducible molecule 14 (Fn14) resulting in cardiomyocyte cell cycle reentry. FGF1\u2010induced cell cycle reentry in neonatal cardiomyocytes could be blocked by Fn14 inhibition, while TWEAK\u2010induced cell cycle activation was inhibited by blocking FGFR\u20101 signaling. In addition, costimulation experiments revealed a synergistic effect of FGF1 and TWEAK in regard to cardiomyocyte cell cycle induction\n                    <jats:italic>via<\/jats:italic>\n                    PI3K\/Akt signaling. Overexpression of Fn14 with either FGFR\u20101 long [FGFR\u20101(L)] or FGFR\u20101 short [FGFR\u20101(S)] isoforms resulted after FGF1\/TWEAK stimulation in cell cycle reentry of &gt;40% adult cardiomyocytes. Finally, coimmunoprecipitation and proximity ligation assays indicated that endogenous FGFR\u20101 and Fn14 interact with each other in cardiomyocytes. This interaction was strongly enhanced in the presence of their corresponding ligands, FGF1 and TWEAK. Taken together, our data suggest that FGFR\u20101\/Fn14 interaction may represent a novel endogenous mechanism to modulate the action of these receptors and their ligands and to control cardiomyocyte cell cycle reentry.\u2014Novoyatleva, T., Sajjad, A., Pogoryelov, D., Patra, C., Schermuly, R. T., Engel, F. B. FGF1\u2010mediated cardiomyocyte cell cycle reentry depends on the interaction of FGFR\u20101 and Fn14.\n                    <jats:italic>FASEB J<\/jats:italic>\n                    . 28, 2492\u20132503 (2014).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.13-243576","type":"journal-article","created":{"date-parts":[[2014,2,27]],"date-time":"2014-02-27T00:11:23Z","timestamp":1393459883000},"page":"2492-2503","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["FGF1\u2010mediated cardiomyocyte cell cycle reentry depends on the interaction of FGFR\u20101 and Fn14"],"prefix":"10.1096","volume":"28","author":[{"given":"Tatyana","family":"Novoyatleva","sequence":"first","affiliation":[{"name":"Department of Cardiac Development and Remodeling Max Planck Institute for Heart and Lung Research Bad Nauheim Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amna","family":"Sajjad","sequence":"additional","affiliation":[{"name":"Department of Cardiac Development and Remodeling Max Planck Institute for Heart and Lung Research Bad Nauheim Germany"},{"name":"Government College University Faisalabad Faisalabad Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Denys","family":"Pogoryelov","sequence":"additional","affiliation":[{"name":"Membrane Transport Machineries Group Cluster of Excellence Frankfurt\u2013Macromolecular Complexes Institute of Biochemistry Goethe University of Frankfurt Frankfurt am Main Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chinmoy","family":"Patra","sequence":"additional","affiliation":[{"name":"Department of Cardiac Development and Remodeling Max Planck Institute for Heart and Lung Research Bad Nauheim Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ralph T.","family":"Schermuly","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Pharmacotherapy Justus Liebig University Giessen Giessen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Felix B.","family":"Engel","sequence":"additional","affiliation":[{"name":"Department of Cardiac Development and Remodeling Max Planck Institute for Heart and Lung Research Bad Nauheim Germany"},{"name":"Experimental Renal and Cardiovascular Research Department of Nephropathology, Institute of Pathology University of Erlangen\u2010N\u00fcrnberg Erlangen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2014,2,26]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/jb\/mvq121"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2780"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000089460.12061.E1"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.copbio.2003.08.003"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd2792"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cytogfr.2005.03.001"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1006\/jmcc.1994.1164"},{"key":"e_1_2_7_9_1","first-page":"H1927","article-title":"Adult cardiomyocytes express functional high-affinity receptors for basic fibroblast growth factor","volume":"268","author":"Liu L.","year":"1995","journal-title":"Am. 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