{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T12:04:49Z","timestamp":1779883489192,"version":"3.53.1"},"reference-count":72,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2024,8,18]],"date-time":"2024-08-18T00:00:00Z","timestamp":1723939200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100012818","name":"Comunidad de Madrid","doi-asserted-by":"publisher","award":["INNOREN P2022\/BMD\u20107221"],"award-info":[{"award-number":["INNOREN P2022\/BMD\u20107221"]}],"id":[{"id":"10.13039\/100012818","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI19\/00502"],"award-info":[{"award-number":["PI19\/00502"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI19\/01339"],"award-info":[{"award-number":["PI19\/01339"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI22\/01714"],"award-info":[{"award-number":["PI22\/01714"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["RD016\/0009\/0018"],"award-info":[{"award-number":["RD016\/0009\/0018"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["RD21\/0005\/0023"],"award-info":[{"award-number":["RD21\/0005\/0023"]}],"id":[{"id":"10.13039\/501100004587","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":[[2024,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>With age, lungs undergo typical changes that lead to a deterioration of respiratory function. Our aim was to assess the role of age\u2010associated hyperphosphatemia in these changes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We used C57BL6 mice to study an ageing model in\u00a0vivo and human lung fibroblasts were treated with a phosphate donor, beta\u2010glycerophosphate (BGP), to explore mechanisms involved. Respiratory function was registered with a double chamber plethysmograph. Lung structure was analysed by different staining, phosphate and cytokines levels by colorimeric kits, expression of fibrosis, inflammation and ET\u20101 system by western blot or RT\u2010PCR.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Old mice showed hyperphosphatemia, along with lung fibrosis, loss of elastin, increased expression of pro\u2010inflammatory cytokines and impaired respiratory function. BGP induced inflammation and fibrosis in fibroblasts through the activation and binding of NF<jats:sc>k<\/jats:sc>B to the MCP\u20101 or FN promoters. BGP increased ECE\u20101 expression by inducing NF<jats:sc>k<\/jats:sc>B binding to the ECE\u20101 promoter. QNZ, an NF<jats:sc>k<\/jats:sc>B inhibitor, blocked these effects. When ECE\u20101 was inhibited with phosphoramidon, BGP\u2010induced inflammation and fibrosis were significantly reduced, suggesting a role for ET\u20101 in BGP\u2010mediated effects.ET\u20101 produced effects similar to those of BGP, which were also dependent on NF<jats:sc>k<\/jats:sc>B. To study the pathophysiological relevance of hyperphosphatemia in\u00a0vivo, a low\u2010P diet was administered to a group of old animals, showing an improvement in fibrosis, inflammation and respiratory function compared to old mice on a standard diet.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These results suggest that age\u2010related hyperphosphatemia induces inflammation, fibrosis, and impaired respiratory function in old mice; these effects appear to be mediated by ET\u20101 and NF<jats:sc>k<\/jats:sc>B activation.<\/jats:p><\/jats:sec>","DOI":"10.1111\/eci.14302","type":"journal-article","created":{"date-parts":[[2024,8,19]],"date-time":"2024-08-19T04:14:06Z","timestamp":1724040846000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Respiratory dysfunction in old mice could be related to inflammation and lung fibrosis induced by hyperphosphatemia"],"prefix":"10.1111","volume":"54","author":[{"given":"Ana","family":"Asenjo\u2010Bueno","sequence":"first","affiliation":[{"name":"Departamento de Biolog\u00eda de Sistemas, Facultad de Medicina y Ciencias de la Salud Universidad de Alcal\u00e1  Alcal\u00e1 de Henares Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Alcalde\u2010Est\u00e9vez","sequence":"additional","affiliation":[{"name":"Departamento de Biolog\u00eda de Sistemas, Facultad de Medicina y Ciencias de la Salud Universidad de Alcal\u00e1  Alcal\u00e1 de Henares Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gemma","family":"Olmos","sequence":"additional","affiliation":[{"name":"Departamento de Biolog\u00eda de Sistemas, Facultad de Medicina y Ciencias de la Salud Universidad de Alcal\u00e1  Alcal\u00e1 de Henares Madrid Spain"},{"name":"Instituto Reina Sof\u00eda de Investigaci\u00f3n Nefrol\u00f3gica (IRSIN) de la Fundaci\u00f3n Renal I\u00f1igo \u00c1lvarez de Toledo (FRIAT)  Madrid Spain"},{"name":"Area 3\u2010Fisiolog\u00eda y Fisiopatolog\u00eda Renal y Vascular del IRYCIS  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Mart\u00ednez\u2010Miguel","sequence":"additional","affiliation":[{"name":"Servicio de Nefrolog\u00eda del Hospital Universitario Pr\u00edncipe de Asturias  Alcal\u00e1 de Henares Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Piedad","family":"Ruiz\u2010Torres","sequence":"additional","affiliation":[{"name":"Departamento de Biolog\u00eda de Sistemas, Facultad de Medicina y Ciencias de la Salud Universidad de Alcal\u00e1  Alcal\u00e1 de Henares Madrid Spain"},{"name":"Instituto Reina Sof\u00eda de Investigaci\u00f3n Nefrol\u00f3gica (IRSIN) de la Fundaci\u00f3n Renal I\u00f1igo \u00c1lvarez de Toledo (FRIAT)  Madrid Spain"},{"name":"Area 3\u2010Fisiolog\u00eda y Fisiopatolog\u00eda Renal y Vascular del IRYCIS  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0045-1680","authenticated-orcid":false,"given":"Susana","family":"L\u00f3pez\u2010Ongil","sequence":"additional","affiliation":[{"name":"Departamento de Biolog\u00eda de Sistemas, Facultad de Medicina y Ciencias de la Salud Universidad de Alcal\u00e1  Alcal\u00e1 de Henares Madrid Spain"},{"name":"Instituto Reina Sof\u00eda de Investigaci\u00f3n Nefrol\u00f3gica (IRSIN) de la Fundaci\u00f3n Renal I\u00f1igo \u00c1lvarez de Toledo (FRIAT)  Madrid Spain"},{"name":"Fundaci\u00f3n para la Investigaci\u00f3n Biom\u00e9dica del Hospital Universitario Pr\u00edncipe de Asturias  Alcal\u00e1 de Henares Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,8,18]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2021.03.005"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.2147\/ciia.2006.1.3.253"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/gerona\/glx090"},{"issue":"6","key":"e_1_2_10_5_1","first-page":"434","article-title":"Age\u2010related physiological changes and their clinical significance","volume":"135","author":"Boss GR","year":"1981","journal-title":"West J Med"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.3389\/fragi.2022.890985"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.13194"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.09-152488"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.18632\/aging.103450"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox10081308"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2008101106"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.12664"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm9082359"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.3164\/jcbn.11-96"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.2277"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00328.2012"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2018.00112"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.115.011833"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000174614.74469.83"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1139\/Y10-059"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2013.12.024"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2015.01.001"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.matbio.2007.06.003"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/gerona\/glaa216"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-08-519520"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exger.2004.01.009"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2015.21"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1093\/gerona\/glu057"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.3791\/57778"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.26355\/eurrev_202002_20387"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.84.7.1876"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.153.5.2052"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.50.29794"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.14336\/AD.2017.1214"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.156.3.9606031"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00561.2002"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.12750"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.05.00035205"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1378\/chest.08-1419"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12931-015-0252-0"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.18632\/aging.204358"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2010.11.013"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-96766-x"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mad.2016.12.008"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2000.tb06651.x"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/692546"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.14336\/AD.2018.0601"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2022.11.001"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1582-4934.2009.00632.x"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1002\/ctm2.1363"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.2174\/187153006779025685"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2796.2008.01953.x"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1998.tb09896.x"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2002-021176"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms141121525"},{"key":"e_1_2_10_56_1","doi-asserted-by":"publisher","DOI":"10.1038\/332411a0"},{"key":"e_1_2_10_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(94)90425-1"},{"key":"e_1_2_10_58_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.cir.102.10.1086"},{"key":"e_1_2_10_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2005.08.012"},{"key":"e_1_2_10_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/0531-5565(91)90010-j"},{"key":"e_1_2_10_61_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvs240"},{"key":"e_1_2_10_62_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000161997.24797.c0"},{"key":"e_1_2_10_63_1","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.167.9.879"},{"key":"e_1_2_10_64_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2008020141"},{"key":"e_1_2_10_65_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2022.870637"},{"key":"e_1_2_10_66_1","doi-asserted-by":"publisher","DOI":"10.1213\/ANE.0000000000002077"},{"key":"e_1_2_10_67_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-023-32053-1"},{"key":"e_1_2_10_68_1","doi-asserted-by":"publisher","DOI":"10.1309\/LMPQ55MG8GXKOFML"},{"key":"e_1_2_10_69_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mad.2010.02.008"},{"key":"e_1_2_10_70_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2008.10.002"},{"key":"e_1_2_10_71_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1112766"},{"key":"e_1_2_10_72_1","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/131.12.3182"},{"key":"e_1_2_10_73_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10571-022-01238-z"}],"container-title":["European Journal of Clinical Investigation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/eci.14302","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,2]],"date-time":"2024-12-02T04:47:09Z","timestamp":1733114829000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/eci.14302"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,18]]},"references-count":72,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2024,12]]}},"alternative-id":["10.1111\/eci.14302"],"URL":"https:\/\/doi.org\/10.1111\/eci.14302","archive":["Portico"],"relation":{},"ISSN":["0014-2972","1365-2362"],"issn-type":[{"value":"0014-2972","type":"print"},{"value":"1365-2362","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8,18]]},"assertion":[{"value":"2024-04-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-08-02","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-08-18","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e14302"}}