{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:47:30Z","timestamp":1787014050633,"version":"build-2736575974"},"reference-count":59,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2022,1,28]],"date-time":"2022-01-28T00:00:00Z","timestamp":1643328000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cell Proliferation"],"published-print":{"date-parts":[[2022,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Endocardial cushions are precursors of the valve septum complex that separates the four heart chambers. Several genes have been implicated in the development of endocardial cushions. Specifically, ERp44 has been found to play a role in the early secretory pathway, but its function in heart development has not been well studied.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>In this study, we established conditional and tissue\u2010specific knockout mouse models. The morphology, survival rate, the development of heart and endocardial cushion were under evaluation. The relationship between ERp44 and VEGFA was investigated by transcriptome, qPCR, WB, immunofluorescence and immunohistochemistry.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      ERp44 knockout (KO) mice were smaller in size, and most mice died during early postnatal life. KO hearts exhibited the typical phenotypes of congenital heart diseases, such as abnormal heart shapes and severe septal and valvular defects. Similar phenotypes were found in\n                      <jats:italic>cTNT<\/jats:italic>\n                      \u2010\n                      <jats:italic>Cre<\/jats:italic>\n                      <jats:sup>+\/\u2212<\/jats:sup>\n                      ;\n                      <jats:italic>\n                        ERp44\n                        <jats:sup>fl<\/jats:sup>\n                      <\/jats:italic>\n                      <jats:sup>\/<\/jats:sup>\n                      <jats:italic>\n                        <jats:sup>fl<\/jats:sup>\n                      <\/jats:italic>\n                      mice, which indicated that myocardial ERp44 principally controls endocardial cushion formation. Further studies demonstrated that the deletion of ERp44 significantly decreased the proliferation of cushion cells and impaired the endocardial\u2010mesenchymal transition (EndMT), which was followed by endocardial cushion dysplasia. Finally, we found that ERp44 was directly bound to VEGFA and controlled its release, further regulating EndMT.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>We demonstrated that ERp44 plays a specific role in heart development. ERp44 contributes to the development of the endocardial cushion by affecting VEGFA\u2010mediated EndMT.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/cpr.13179","type":"journal-article","created":{"date-parts":[[2022,1,28]],"date-time":"2022-01-28T05:42:13Z","timestamp":1643348533000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["ERp44 is required for endocardial cushion development by regulating VEGFA secretion in myocardium"],"prefix":"10.1111","volume":"55","author":[{"given":"Youkun","family":"Bi","sequence":"first","affiliation":[{"name":"Key Laboratory of Interdisciplinary Research Institute of Biophysics Chinese Academy of Sciences Beijing China"},{"name":"University of Chinese Academy of Sciences Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiguang","family":"Yang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Interdisciplinary Research 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