{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T23:02:03Z","timestamp":1790550123547,"version":"4.1.0"},"reference-count":40,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2021,3,17]],"date-time":"2021-03-17T00:00:00Z","timestamp":1615939200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["190538538"],"award-info":[{"award-number":["190538538"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["374031971"],"award-info":[{"award-number":["374031971"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Eur J Clin Investigation"],"published-print":{"date-parts":[[2021,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Gremlin\u20101 is a cystine knot protein and is expressed in organs developing fibrosis. Transient ischaemia leads to myocardial fibrosis, a major determinant of impaired myocardial function.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and methods<\/jats:title>\n                    <jats:p>Expression of Gremlin\u20101 was investigated in infarcted myocardium by real\u2010time PCR, Western blot analysis, histological and immunohistochemistry staining. We further elaborated the colocalization of Gremlin\u20101 and TGF\u2010\u03b2 proteins by confocal microscopy and co\u2010immunoprecipitation experiments. The interaction between Gremlin\u20101 and TGF\u2010\u03b2 was analysed by photon correlation spectroscopy. Gremlin\u20101 modulation of the TGF\u2010\u03b2\u2010dependent collagen I synthesis in fibroblasts was investigated using ELISA and immunohistochemistry experiments. The effect of prolonged administration of recombinant Gremlin\u20101 on myocardial function following ischaemia\/reperfusion was accessed by echocardiography and immunohistochemistry.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Gremlin\u20101 is expressed in myocardial tissue and infiltrating cells after transient myocardial ischaemia (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&lt;\u00a0.05). Gremlin\u20101 colocalizes with the pro\u2010fibrotic cytokine transforming growth factor\u2010\u03b2 (TGF\u2010\u03b2) expressed in fibroblasts and inflammatory cell infiltrates (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&lt;\u00a0.05). Gremlin\u20101 reduces TGF\u2010\u03b2\u2010induced collagen production of myocardial fibroblasts by approximately 20% (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&lt;\u00a0.05). We found that Gremlin\u20101 binds with high affinity to TGF\u2010\u03b2 (\n                      <jats:italic>K<\/jats:italic>\n                      <jats:sub>D<\/jats:sub>\n                      \u00a0=\u00a054\u00a0nmol\/L) as evidenced by photon correlation spectroscopy and co\u2010immunoprecipitation. intravenous administration of\n                      <jats:sub>m<\/jats:sub>\n                      Gremlin\u20101\u2010Fc, but not of equivalent amount of Fc control, significantly reduced infarct size by approximately 20%. In the\n                      <jats:sub>m<\/jats:sub>\n                      Gremlin\u20101\u2010Fc group, infarct area was reduced by up to 30% in comparison with mice treated with Fc control (I\/LV: 4.8\u00a0\u00b1\u00a01.2% vs 6.0\u00a0\u00b1\u00a01.2%\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&lt;\u00a0.05; I\/AaR: 15.2\u00a0\u00b1\u00a01.5% vs 21.1\u00a0\u00b1\u00a05%,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&lt;\u00a0.05).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The present data disclose Gremlin\u20101 as an antagonist of TGF\u2010\u03b2 and presume a role for Gremlin\u20101\/TGF\u2010\u03b2 interaction in myocardial remodelling following myocardial ischaemia.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/eci.13539","type":"journal-article","created":{"date-parts":[[2021,3,17]],"date-time":"2021-03-17T09:04:11Z","timestamp":1615971851000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Protective role of Gremlin\u20101 in myocardial function"],"prefix":"10.1111","volume":"51","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2101-1633","authenticated-orcid":false,"given":"Iris I.","family":"M\u00fcller","sequence":"first","affiliation":[{"name":"Department of Cardiology and Angiology University Hospital Eberhard Karls University of Tuebingen Tuebingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Schneider","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Angiology University Hospital Eberhard Karls University of Tuebingen Tuebingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karin A. L.","family":"M\u00fcller","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Angiology University Hospital Eberhard Karls University of Tuebingen Tuebingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oleg","family":"Lunov","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology of Natural Products &amp; Clinical Pharmacology Ulm University Ulm Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver","family":"Borst","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Angiology University Hospital Eberhard Karls University of Tuebingen Tuebingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Simmet","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology of Natural Products &amp; Clinical Pharmacology Ulm University Ulm Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1124-9592","authenticated-orcid":false,"given":"Meinrad","family":"Gawaz","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Angiology University Hospital Eberhard Karls University of Tuebingen Tuebingen 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