{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T18:59:09Z","timestamp":1785437949069,"version":"3.56.0"},"reference-count":67,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T00:00:00Z","timestamp":1778457600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Kerckhoff Foundation"},{"DOI":"10.13039\/501100008436","name":"Ernst and Berta Grimmke Foundation","doi-asserted-by":"crossref","award":["15\/24 I.Z. 627800329"],"award-info":[{"award-number":["15\/24 I.Z. 627800329"]}],"id":[{"id":"10.13039\/501100008436","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Association of Friends and Supporters of the Kerckhoff Clinic","award":["974119"],"award-info":[{"award-number":["974119"]}]},{"name":"SFB 1213"},{"name":"DFG"},{"id":[{"id":"https:\/\/ror.org\/05v8e1c02","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Postnatal loss of cardiac regenerative capacity coincides with profound remodeling of signaling, structural, and metabolic programs in the developing heart. Here, we profiled Insulin growth factor (IGF)\/Fibrobrast growth factor (FGF)\/insulin receptors (InsR), Ras\/Raf\/MEK\/ERK pathway components, cytoskeletal markers, and cell-cycle\/metabolic proteins in mouse whole-heart tissue at P3, P7, P14, P28, and adulthood. IGF-1R- and IGF-2R-associated signals declined sharply during maturation, whereas InsR changed more modestly. FGFR1-derived immunoreactive species showed a transient early postnatal increase before marked reduction at later stages. These receptor-associated changes paralleled strong decreases in B-Raf, MEK1, and MEK2, together with pronounced loss of MEK1\/2 activation-loop phosphorylation. MEK1 Thr292 phosphorylation also declined markedly, identifying a previously unrecognized developmental phosphorylation pattern. Structural maturation was accompanied by stable Actn2 expression, downregulation of immature cytoskeletal markers, increased cytochrome c and myoglobin, and significant loss of Aurora B and phospho-histone H3 in adult hearts. Together, these findings describe a coordinated postnatal maturation program in which signaling, cytoskeletal remodeling, metabolism, and proliferative withdrawal change in parallel. These data are consistent with reduced MAPK pathway activity during maturation and highlighting this signaling as node associated with closure of the neonatal regenerative window.<\/jats:p>","DOI":"10.3390\/cells15100873","type":"journal-article","created":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T06:42:18Z","timestamp":1779691338000},"page":"873","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Coordinated Developmental Remodeling of IGF\/FGF\u2013MAPK Signaling and Cytoskeletal Plasticity Coincides with the Loss of Cardiac Regenerative Capacity"],"prefix":"10.3390","volume":"15","author":[{"given":"Natalia","family":"Kubin","sequence":"first","affiliation":[{"name":"Department of Cardiology, Kerckhoff Campus, Justus Liebig University, 61231 Bad Nauheim, Germany"},{"name":"Medical Clinic I, Department of Cardiology and Angiology, Justus Liebig University, 35392 Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1212-5404","authenticated-orcid":false,"given":"Praveen","family":"Gajawada","sequence":"additional","affiliation":[{"name":"Department of Cardiac Surgery, Kerckhoff Heart Center, 61231 Bad Nauheim, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-0776-3508","authenticated-orcid":false,"given":"Thomas","family":"K\u00f6rtl","sequence":"additional","affiliation":[{"name":"Medical Clinic I, Department of Cardiology and Angiology, Justus Liebig University, 35392 Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-2715-8345","authenticated-orcid":false,"given":"Andre","family":"Schneider","sequence":"additional","affiliation":[{"name":"Max-Planck-Institute for Heart and Lung Research, 61231 Bad Nauheim, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Han","sequence":"additional","affiliation":[{"name":"Max-Planck-Institute for Heart and Lung Research, 61231 Bad Nauheim, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9001-0346","authenticated-orcid":false,"given":"Laura C.","family":"Zelaray\u00e1n","sequence":"additional","affiliation":[{"name":"Medical Clinic I, Department of Cardiology and Angiology, Justus Liebig University, 35392 Giessen, Germany"},{"name":"Institute of Pharmacology & Toxicology, University Medical Center G\u00f6ttingen, 37075 G\u00f6ttingen, Germany"},{"name":"German Centre for Cardiovascular Research (DZHK), partner sites Lower Saxony, 37099 G\u00f6ttingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6165-4804","authenticated-orcid":false,"given":"Thomas","family":"Braun","sequence":"additional","affiliation":[{"name":"Max-Planck-Institute for Heart and Lung Research, 61231 Bad Nauheim, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel","family":"Sossalla","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Kerckhoff Campus, Justus Liebig University, 61231 Bad Nauheim, Germany"},{"name":"Medical Clinic I, Department of Cardiology and Angiology, Justus Liebig University, 35392 Giessen, Germany"},{"name":"German Centre for Cardiovascular Research (DZHK), partner sites Lower Saxony, 37099 G\u00f6ttingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yeong-Hoon","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Cardiac Surgery, Kerckhoff Heart Center, 61231 Bad Nauheim, Germany"},{"name":"German Centre for Cardiovascular Research (DZHK), partner sites Lower Saxony, 37099 G\u00f6ttingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6239-3503","authenticated-orcid":false,"given":"Manfred","family":"Richter","sequence":"additional","affiliation":[{"name":"Department of Cardiac Surgery, Kerckhoff Heart Center, 61231 Bad Nauheim, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1535","DOI":"10.1016\/S0003-4975(02)04822-1","article-title":"Anatomic repair of anomalous left coronary artery from the pulmonary artery by aortic reimplantation: Early survival, patterns of ventricular recovery and late outcome","volume":"75","author":"Azakie","year":"2003","journal-title":"Ann. 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