{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T18:16:36Z","timestamp":1791224196115,"version":"4.1.0"},"reference-count":48,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2011,4]]},"abstract":"<jats:sec>\n                    <jats:title>Objective\u2014<\/jats:title>\n                    <jats:p>Prokineticins are potent angiogenic hormones that use 2 receptors, prokineticin receptor-1 (PKR1) and PKR2, with important therapeutic use in anticancer therapy. Observations of cardiac and renal toxicity in cancer patients treated with antiangiogenic compounds led us to explore how PKR1 signaling functioned in heart and kidney in vivo.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and Results\u2014<\/jats:title>\n                    <jats:p>We generated mice with a conditional disruption of the PKR1 gene. We observed that PKR1 loss led to cardiomegaly, severe interstitial fibrosis, and cardiac dysfunction under stress conditions, accompanied by renal tubular dilation, reduced glomerular capillaries, urinary phosphate excretion, and proteinuria at later ages. Abnormal mitochondria and increased apoptosis were evident in both organs. Perturbation of capillary angiogenesis in both organs was restored at the adult stage potentially via upregulation of hypoxia-inducible factor-1 and proangiogenic factors. Compensatory mechanism could not revoke the epicardial and glomerular capillary networks, because of increased apoptosis and reduced progenitor cell numbers, consistent with an endogenous role of PKR1 signaling in stimulating epicardin+ progenitor cell proliferation and differentiation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion\u2014<\/jats:title>\n                    <jats:p>Here, we showed for the first time that the loss of PKR1 causes renal and cardiac structural and functional changes because of deficits in survival signaling, mitochondrial, and progenitor cell functions in found both organs.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/atvbaha.110.222323","type":"journal-article","created":{"date-parts":[[2011,1,27]],"date-time":"2011-01-27T23:44:32Z","timestamp":1296171872000},"page":"842-850","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":29,"title":["Genetic Inactivation of Prokineticin Receptor-1 Leads to Heart and Kidney Disorders"],"prefix":"10.1161","volume":"31","author":[{"given":"Mounia","family":"Boulberdaa","sequence":"first","affiliation":[{"name":"From the Centre National de la Recherche Scientifique, Universit\u00e9 de Strasbourg, UMR 7242, Ecole Sup\u00e9rieure de Biotechnologie de Strasbourg, Illkirch, France (M.B., G.T., K.U., M.D., C.S., C.G.N.); Center of Exploration and Research Multimodel and Pluridisiplinary, Imagerie du vivant and Universit\u00e9 Lyon 1 (L.Z.); Institut de G\u00e9n\u00e9tique et de Biologie Mol\u00e9culaire et Cellulaire, UMR 7104 Centre National de la Recherche Scientifique, U964 Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gulen","family":"Turkeri","sequence":"additional","affiliation":[{"name":"From the Centre National de la Recherche Scientifique, Universit\u00e9 de Strasbourg, UMR 7242, Ecole Sup\u00e9rieure de Biotechnologie de Strasbourg, Illkirch, France (M.B., G.T., K.U., M.D., C.S., C.G.N.); Center of Exploration and Research Multimodel and Pluridisiplinary, Imagerie du vivant and Universit\u00e9 Lyon 1 (L.Z.); Institut de G\u00e9n\u00e9tique et de Biologie Mol\u00e9culaire et Cellulaire, UMR 7104 Centre National de la Recherche Scientifique, U964 Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyoji","family":"Urayama","sequence":"additional","affiliation":[{"name":"From the Centre National de la Recherche Scientifique, Universit\u00e9 de Strasbourg, UMR 7242, Ecole Sup\u00e9rieure de Biotechnologie de Strasbourg, Illkirch, France (M.B., G.T., K.U., M.D., C.S., C.G.N.); Center of Exploration and Research Multimodel and Pluridisiplinary, Imagerie du vivant and Universit\u00e9 Lyon 1 (L.Z.); Institut de G\u00e9n\u00e9tique et de Biologie Mol\u00e9culaire et Cellulaire, UMR 7104 Centre National de la Recherche Scientifique, U964 Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mojdeh","family":"Dormishian","sequence":"additional","affiliation":[{"name":"From the Centre National de la Recherche Scientifique, Universit\u00e9 de Strasbourg, UMR 7242, Ecole Sup\u00e9rieure de Biotechnologie de Strasbourg, Illkirch, France (M.B., G.T., K.U., M.D., C.S., C.G.N.); Center of Exploration and Research Multimodel and Pluridisiplinary, Imagerie du vivant and Universit\u00e9 Lyon 1 (L.Z.); Institut de G\u00e9n\u00e9tique et de Biologie Mol\u00e9culaire et Cellulaire, UMR 7104 Centre National de la Recherche Scientifique, U964 Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9cilia","family":"Szatkowski","sequence":"additional","affiliation":[{"name":"From the Centre National de la Recherche Scientifique, Universit\u00e9 de Strasbourg, UMR 7242, Ecole Sup\u00e9rieure de Biotechnologie de Strasbourg, Illkirch, France (M.B., G.T., K.U., M.D., C.S., C.G.N.); Center of Exploration and Research Multimodel and Pluridisiplinary, Imagerie du vivant and Universit\u00e9 Lyon 1 (L.Z.); Institut de G\u00e9n\u00e9tique et de Biologie Mol\u00e9culaire et Cellulaire, UMR 7104 Centre National de la Recherche Scientifique, U964 Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luc","family":"Zimmer","sequence":"additional","affiliation":[{"name":"From the Centre National de la Recherche Scientifique, Universit\u00e9 de Strasbourg, UMR 7242, Ecole Sup\u00e9rieure de Biotechnologie de Strasbourg, Illkirch, France (M.B., G.T., K.U., M.D., C.S., C.G.N.); Center of Exploration and Research Multimodel and Pluridisiplinary, Imagerie du vivant and Universit\u00e9 Lyon 1 (L.Z.); Institut de G\u00e9n\u00e9tique et de Biologie Mol\u00e9culaire et Cellulaire, UMR 7104 Centre National de la Recherche Scientifique, U964 Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadia","family":"Messaddeq","sequence":"additional","affiliation":[{"name":"From the Centre National de la Recherche Scientifique, Universit\u00e9 de Strasbourg, UMR 7242, Ecole Sup\u00e9rieure de Biotechnologie de Strasbourg, Illkirch, France (M.B., G.T., K.U., M.D., C.S., C.G.N.); Center of Exploration and Research Multimodel and Pluridisiplinary, Imagerie du vivant and Universit\u00e9 Lyon 1 (L.Z.); Institut de G\u00e9n\u00e9tique et de Biologie Mol\u00e9culaire et Cellulaire, UMR 7104 Centre National de la Recherche Scientifique, U964 Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Virginie","family":"Laugel","sequence":"additional","affiliation":[{"name":"From the Centre National de la Recherche Scientifique, Universit\u00e9 de Strasbourg, UMR 7242, Ecole Sup\u00e9rieure de Biotechnologie de Strasbourg, Illkirch, France (M.B., G.T., K.U., M.D., C.S., C.G.N.); Center of Exploration and Research Multimodel and Pluridisiplinary, Imagerie du vivant and Universit\u00e9 Lyon 1 (L.Z.); Institut de G\u00e9n\u00e9tique et de Biologie Mol\u00e9culaire et Cellulaire, UMR 7104 Centre National de la Recherche Scientifique, U964 Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascal","family":"Doll\u00e9","sequence":"additional","affiliation":[{"name":"From the Centre National de la Recherche Scientifique, Universit\u00e9 de Strasbourg, UMR 7242, Ecole Sup\u00e9rieure de Biotechnologie de Strasbourg, Illkirch, France (M.B., G.T., K.U., M.D., C.S., C.G.N.); 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