{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T05:39:01Z","timestamp":1777873141694,"version":"3.51.4"},"reference-count":65,"publisher":"Frontiers Media SA","issue":"1","license":[{"start":{"date-parts":[[2019,12,17]],"date-time":"2019-12-17T00:00:00Z","timestamp":1576540800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"publisher","award":["88881.132370\/2016-01"],"award-info":[{"award-number":["88881.132370\/2016-01"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Exp Biol Med (Maywood)"],"published-print":{"date-parts":[[2020,1]]},"abstract":"<jats:p>In chronic kidney disease (CKD), evidence suggests that soluble \u03b1Klotho (sKlotho) has cardioprotective effects. Contrariwise, high circulating levels of fibroblast growth factor 23 (FGF23) are related to uremic cardiomyopathy development. Recently, it has been demonstrated that sKlotho can act as a soluble FGF23 co-receptor, allowing sKlotho to modulate FGF23 actions in the myocardium, leading to the activation of cardioprotective pathways. Fibroblast growth factor 21 (FGF21) is a cardiomyokine with sKlotho-like protective actions and has never been evaluated in uremic cardiomyopathy. Here, we aimed to evaluate whether recombinant \u03b1Klotho (rKlotho) replacement can attenuate cardiac remodeling in an established uremic cardiomyopathy, and to explore its impact on myocardial FGF21 expression. Forty-six male Wistar rats were divided into three groups: control, CKD-untreated, and CKD treated with rKlotho (CKD\u2009+\u2009KL). CKD was induced by 5\/6 nephrectomy. From weeks 4\u20138, the control and CKD-untreated groups received vehicle, whereas the CKD\u2009+\u2009KL group received subcutaneous rKlotho replacement (0.01\u2009mg\/kg) every 48\u2009h. Myocardial remodeling was evaluated by heart weight\/tibia length (HW\/TL) ratio, echocardiographic parameters, myocardial histomorphometry, and myocardial expression of \u03b2-myosin heavy chain (MHC\u03b2), alpha smooth muscle actin (\u03b1SMA), transient receptor potential cation channel 6 (TRPC6), and FGF21. As expected, CKD animals had reduced levels of sKlotho and increased serum FGF23 levels. Compared to the control group, manifest myocardial remodeling was present in the CKD-untreated group, while it was attenuated in the CKD\u2009+\u2009KL group. Furthermore, cardiomyocyte diameter and interstitial fibrotic area were reduced in the CKD\u2009+\u2009KL group compared to the CKD-untreated group. Similarly, rKlotho replacement was associated with reduced myocardial expression of TRPC6, MHC\u03b2, and \u03b1SMA and a higher expression of FGF21. rKlotho showed cardioprotective effects by attenuating myocardial remodeling and reducing TRPC6 expression. Interestingly, rKlotho replacement was also associated with increased myocardial FGF21 expression, suggesting that an interaction between the two cardioprotective pathways needs to be further explored.<\/jats:p>\n                  <jats:sec>\n                    <jats:title>Impact statement<\/jats:title>\n                    <jats:p>This study aimed to evaluate whether rKlotho replacement can attenuate cardiac remodeling in a post-disease onset therapeutic reasoning and explore the impact on myocardial FGF21 expression. This study contributes significantly to the literature, as the therapeutic effects of rKlotho replacement and FGF21 myocardial expression have not been widely evaluated in a setting of uremic cardiomyopathy. For the first time, it has been demonstrated that subcutaneous rKlotho replacement may attenuate cardiac remodeling in established uremic cardiomyopathy and increase myocardial expression of FGF21, suggesting a correlation between \u03b1Klotho and myocardial FGF21 expression. The possibility of interaction between the \u03b1Klotho and FGF21 cardioprotective pathways needs to be further explored, but, if confirmed, would point to a therapeutic potential of FGF21 in uremic cardiomyopathy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/1535370219894302","type":"journal-article","created":{"date-parts":[[2019,12,18]],"date-time":"2019-12-18T00:31:37Z","timestamp":1576629097000},"page":"66-78","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":11,"title":["\u03b1Klotho attenuates cardiac hypertrophy and increases myocardial fibroblast growth factor 21 expression in uremic rats"],"prefix":"10.3389","volume":"245","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9123-9564","authenticated-orcid":false,"given":"Paulo Giovani de Albuquerque","family":"Suassuna","sequence":"first","affiliation":[{"name":"Laboratory of Experimental Nephrology (LABNEX) and Interdisciplinary Nucleus of Laboratory Animal Studies (NIDEAL), Federal University of Juiz de Fora (UFJF), Juiz de Fora, Minas Gerais 36036-900, Brazil"},{"name":"Interdisciplinary Center for Studies, Research and Treatment in Nephrology (NIEPEN), Federal University of Juiz de Fora, Juiz de Fora, Minas Gerais 36036-900, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paula Marocolo","family":"Cherem","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Nephrology (LABNEX) and Interdisciplinary Nucleus of Laboratory Animal Studies (NIDEAL), Federal University of Juiz de Fora (UFJF), Juiz de Fora, Minas Gerais 36036-900, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B\u00e1rbara Bruna","family":"de Castro","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Nephrology (LABNEX) and Interdisciplinary Nucleus of Laboratory Animal Studies (NIDEAL), Federal University of Juiz de Fora (UFJF), Juiz de Fora, Minas Gerais 36036-900, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edgar","family":"Maquigussa","sequence":"additional","affiliation":[{"name":"Nephrology Division, Department of Medicine, Federal University of S\u00e3o Paulo, S\u00e3o Paulo 04024-002, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marco Antonio","family":"Cenedeze","sequence":"additional","affiliation":[{"name":"Nephrology Division, Department of Medicine, Federal University of S\u00e3o Paulo, S\u00e3o Paulo 04024-002, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J\u00falio Cesar Moraes","family":"Lovisi","sequence":"additional","affiliation":[{"name":"Interdisciplinary Center for Studies, Research and Treatment in Nephrology (NIEPEN), Federal University of Juiz de Fora, Juiz de Fora, Minas Gerais 36036-900, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melani Ribeiro","family":"Cust\u00f3dio","sequence":"additional","affiliation":[{"name":"Nephrology Division, Department of Medicine, University of S\u00e3o Paulo, S\u00e3o Paulo 01246-903, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8603-1331","authenticated-orcid":false,"given":"Helady","family":"Sanders-Pinheiro","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Nephrology (LABNEX) and Interdisciplinary Nucleus of Laboratory Animal Studies (NIDEAL), Federal University of Juiz de Fora (UFJF), Juiz de Fora, Minas Gerais 36036-900, Brazil"},{"name":"Interdisciplinary Center for Studies, Research and Treatment in Nephrology (NIEPEN), Federal University of Juiz de Fora, Juiz de Fora, Minas Gerais 36036-900, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rog\u00e9rio Baumgratz","family":"de Paula","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Nephrology 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