{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T22:36:05Z","timestamp":1792794965721,"version":"4.5.0"},"reference-count":46,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2023,3,9]],"date-time":"2023-03-09T00:00:00Z","timestamp":1678320000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fondo Europeo de Desarrollo Regional (FEDER)","award":["GRUPIN 14-028"],"award-info":[{"award-number":["GRUPIN 14-028"]}]},{"name":"Fondo Europeo de Desarrollo Regional (FEDER)","award":["IDI-2018-000-152"],"award-info":[{"award-number":["IDI-2018-000-152"]}]},{"name":"Fondo Europeo de Desarrollo Regional (FEDER)","award":["IDI\/2021\/000080"],"award-info":[{"award-number":["IDI\/2021\/000080"]}]},{"name":"Fondo Europeo de Desarrollo Regional (FEDER)","award":["RD12\/0021\/1023"],"award-info":[{"award-number":["RD12\/0021\/1023"]}]},{"name":"Fondo Europeo de Desarrollo Regional (FEDER)","award":["RD16\/0009\/0017"],"award-info":[{"award-number":["RD16\/0009\/0017"]}]},{"name":"Fondo Europeo de Desarrollo Regional (FEDER)","award":["RD21\/0005\/0019"],"award-info":[{"award-number":["RD21\/0005\/0019"]}]},{"name":"Fondo Europeo de Desarrollo Regional (FEDER)","award":["PI17\/00384"],"award-info":[{"award-number":["PI17\/00384"]}]},{"name":"Fondo Europeo de Desarrollo Regional (FEDER)","award":["PI19\/00532"],"award-info":[{"award-number":["PI19\/00532"]}]},{"name":"Fondo Europeo de Desarrollo Regional (FEDER)","award":["PI20\/00753"],"award-info":[{"award-number":["PI20\/00753"]}]},{"name":"Fondo Europeo de Desarrollo Regional (FEDER)","award":["PI20\/00633"],"award-info":[{"award-number":["PI20\/00633"]}]},{"name":"Fondo Europeo de Desarrollo Regional (FEDER)","award":["BP19-057"],"award-info":[{"award-number":["BP19-057"]}]},{"name":"Fondo Europeo de Desarrollo Regional (FEDER)","award":["BP20-081"],"award-info":[{"award-number":["BP20-081"]}]},{"name":"Fondo Europeo de Desarrollo Regional (FEDER)","award":["FPU2019-00483"],"award-info":[{"award-number":["FPU2019-00483"]}]},{"name":"Instituto de Salud Carlos III","award":["GRUPIN 14-028"],"award-info":[{"award-number":["GRUPIN 14-028"]}]},{"name":"Instituto de Salud Carlos III","award":["IDI-2018-000-152"],"award-info":[{"award-number":["IDI-2018-000-152"]}]},{"name":"Instituto de Salud Carlos III","award":["IDI\/2021\/000080"],"award-info":[{"award-number":["IDI\/2021\/000080"]}]},{"name":"Instituto de Salud Carlos III","award":["RD12\/0021\/1023"],"award-info":[{"award-number":["RD12\/0021\/1023"]}]},{"name":"Instituto de Salud Carlos III","award":["RD16\/0009\/0017"],"award-info":[{"award-number":["RD16\/0009\/0017"]}]},{"name":"Instituto de Salud Carlos III","award":["RD21\/0005\/0019"],"award-info":[{"award-number":["RD21\/0005\/0019"]}]},{"name":"Instituto de Salud Carlos III","award":["PI17\/00384"],"award-info":[{"award-number":["PI17\/00384"]}]},{"name":"Instituto de Salud Carlos III","award":["PI19\/00532"],"award-info":[{"award-number":["PI19\/00532"]}]},{"name":"Instituto de Salud Carlos III","award":["PI20\/00753"],"award-info":[{"award-number":["PI20\/00753"]}]},{"name":"Instituto de Salud Carlos III","award":["PI20\/00633"],"award-info":[{"award-number":["PI20\/00633"]}]},{"name":"Instituto de Salud Carlos III","award":["BP19-057"],"award-info":[{"award-number":["BP19-057"]}]},{"name":"Instituto de Salud Carlos III","award":["BP20-081"],"award-info":[{"award-number":["BP20-081"]}]},{"name":"Instituto de Salud Carlos III","award":["FPU2019-00483"],"award-info":[{"award-number":["FPU2019-00483"]}]},{"name":"Instituto de Salud Carlos III and co-funded by the by European Regional Development Fund\/European Social Fund","award":["GRUPIN 14-028"],"award-info":[{"award-number":["GRUPIN 14-028"]}]},{"name":"Instituto de Salud Carlos III and co-funded by the by European Regional Development Fund\/European Social Fund","award":["IDI-2018-000-152"],"award-info":[{"award-number":["IDI-2018-000-152"]}]},{"name":"Instituto de Salud Carlos III and co-funded by the by European Regional Development Fund\/European Social Fund","award":["IDI\/2021\/000080"],"award-info":[{"award-number":["IDI\/2021\/000080"]}]},{"name":"Instituto de Salud Carlos III and co-funded by the by European Regional Development Fund\/European Social Fund","award":["RD12\/0021\/1023"],"award-info":[{"award-number":["RD12\/0021\/1023"]}]},{"name":"Instituto de Salud Carlos III and co-funded by the by European Regional Development Fund\/European Social Fund","award":["RD16\/0009\/0017"],"award-info":[{"award-number":["RD16\/0009\/0017"]}]},{"name":"Instituto de Salud Carlos III and co-funded by the by European Regional Development Fund\/European Social Fund","award":["RD21\/0005\/0019"],"award-info":[{"award-number":["RD21\/0005\/0019"]}]},{"name":"Instituto de Salud Carlos III and co-funded by the by European Regional Development Fund\/European Social Fund","award":["PI17\/00384"],"award-info":[{"award-number":["PI17\/00384"]}]},{"name":"Instituto de Salud Carlos III and co-funded by the by European Regional Development Fund\/European Social Fund","award":["PI19\/00532"],"award-info":[{"award-number":["PI19\/00532"]}]},{"name":"Instituto de Salud Carlos III and co-funded by the by European Regional Development Fund\/European Social Fund","award":["PI20\/00753"],"award-info":[{"award-number":["PI20\/00753"]}]},{"name":"Instituto de Salud Carlos III and co-funded by the by European Regional Development Fund\/European Social Fund","award":["PI20\/00633"],"award-info":[{"award-number":["PI20\/00633"]}]},{"name":"Instituto de Salud Carlos III and co-funded by the by European Regional Development Fund\/European Social Fund","award":["BP19-057"],"award-info":[{"award-number":["BP19-057"]}]},{"name":"Instituto de Salud Carlos III and co-funded by the by European Regional Development Fund\/European Social Fund","award":["BP20-081"],"award-info":[{"award-number":["BP20-081"]}]},{"name":"Instituto de Salud Carlos III and co-funded by the by European Regional Development Fund\/European Social Fund","award":["FPU2019-00483"],"award-info":[{"award-number":["FPU2019-00483"]}]},{"name":"Gobierno del Principado de Asturias (\u201cSevero Ochoa\u201d program)","award":["GRUPIN 14-028"],"award-info":[{"award-number":["GRUPIN 14-028"]}]},{"name":"Gobierno del Principado de Asturias (\u201cSevero Ochoa\u201d program)","award":["IDI-2018-000-152"],"award-info":[{"award-number":["IDI-2018-000-152"]}]},{"name":"Gobierno del Principado de Asturias (\u201cSevero Ochoa\u201d program)","award":["IDI\/2021\/000080"],"award-info":[{"award-number":["IDI\/2021\/000080"]}]},{"name":"Gobierno del Principado de Asturias (\u201cSevero Ochoa\u201d program)","award":["RD12\/0021\/1023"],"award-info":[{"award-number":["RD12\/0021\/1023"]}]},{"name":"Gobierno del Principado de Asturias (\u201cSevero Ochoa\u201d program)","award":["RD16\/0009\/0017"],"award-info":[{"award-number":["RD16\/0009\/0017"]}]},{"name":"Gobierno del Principado de Asturias (\u201cSevero Ochoa\u201d program)","award":["RD21\/0005\/0019"],"award-info":[{"award-number":["RD21\/0005\/0019"]}]},{"name":"Gobierno del Principado de Asturias (\u201cSevero Ochoa\u201d program)","award":["PI17\/00384"],"award-info":[{"award-number":["PI17\/00384"]}]},{"name":"Gobierno del Principado de Asturias (\u201cSevero Ochoa\u201d program)","award":["PI19\/00532"],"award-info":[{"award-number":["PI19\/00532"]}]},{"name":"Gobierno del Principado de Asturias (\u201cSevero Ochoa\u201d program)","award":["PI20\/00753"],"award-info":[{"award-number":["PI20\/00753"]}]},{"name":"Gobierno del Principado de Asturias (\u201cSevero Ochoa\u201d program)","award":["PI20\/00633"],"award-info":[{"award-number":["PI20\/00633"]}]},{"name":"Gobierno del Principado de Asturias (\u201cSevero Ochoa\u201d program)","award":["BP19-057"],"award-info":[{"award-number":["BP19-057"]}]},{"name":"Gobierno del Principado de Asturias (\u201cSevero Ochoa\u201d program)","award":["BP20-081"],"award-info":[{"award-number":["BP20-081"]}]},{"name":"Gobierno del Principado de Asturias (\u201cSevero Ochoa\u201d program)","award":["FPU2019-00483"],"award-info":[{"award-number":["FPU2019-00483"]}]},{"name":"Ministerio de Ciencia, Innovaci\u00f3n y Universidades (FPU program)","award":["GRUPIN 14-028"],"award-info":[{"award-number":["GRUPIN 14-028"]}]},{"name":"Ministerio de Ciencia, Innovaci\u00f3n y Universidades (FPU program)","award":["IDI-2018-000-152"],"award-info":[{"award-number":["IDI-2018-000-152"]}]},{"name":"Ministerio de Ciencia, Innovaci\u00f3n y Universidades (FPU program)","award":["IDI\/2021\/000080"],"award-info":[{"award-number":["IDI\/2021\/000080"]}]},{"name":"Ministerio de Ciencia, Innovaci\u00f3n y Universidades (FPU program)","award":["RD12\/0021\/1023"],"award-info":[{"award-number":["RD12\/0021\/1023"]}]},{"name":"Ministerio de Ciencia, Innovaci\u00f3n y Universidades (FPU program)","award":["RD16\/0009\/0017"],"award-info":[{"award-number":["RD16\/0009\/0017"]}]},{"name":"Ministerio de Ciencia, Innovaci\u00f3n y Universidades (FPU program)","award":["RD21\/0005\/0019"],"award-info":[{"award-number":["RD21\/0005\/0019"]}]},{"name":"Ministerio de Ciencia, Innovaci\u00f3n y Universidades (FPU program)","award":["PI17\/00384"],"award-info":[{"award-number":["PI17\/00384"]}]},{"name":"Ministerio de Ciencia, Innovaci\u00f3n y Universidades (FPU program)","award":["PI19\/00532"],"award-info":[{"award-number":["PI19\/00532"]}]},{"name":"Ministerio de Ciencia, Innovaci\u00f3n y Universidades (FPU program)","award":["PI20\/00753"],"award-info":[{"award-number":["PI20\/00753"]}]},{"name":"Ministerio de Ciencia, Innovaci\u00f3n y Universidades (FPU program)","award":["PI20\/00633"],"award-info":[{"award-number":["PI20\/00633"]}]},{"name":"Ministerio de Ciencia, Innovaci\u00f3n y Universidades (FPU program)","award":["BP19-057"],"award-info":[{"award-number":["BP19-057"]}]},{"name":"Ministerio de Ciencia, Innovaci\u00f3n y Universidades (FPU program)","award":["BP20-081"],"award-info":[{"award-number":["BP20-081"]}]},{"name":"Ministerio de Ciencia, Innovaci\u00f3n y Universidades (FPU program)","award":["FPU2019-00483"],"award-info":[{"award-number":["FPU2019-00483"]}]},{"name":"RICORS2040 (Kidney Disease)","award":["GRUPIN 14-028"],"award-info":[{"award-number":["GRUPIN 14-028"]}]},{"name":"RICORS2040 (Kidney Disease)","award":["IDI-2018-000-152"],"award-info":[{"award-number":["IDI-2018-000-152"]}]},{"name":"RICORS2040 (Kidney Disease)","award":["IDI\/2021\/000080"],"award-info":[{"award-number":["IDI\/2021\/000080"]}]},{"name":"RICORS2040 (Kidney Disease)","award":["RD12\/0021\/1023"],"award-info":[{"award-number":["RD12\/0021\/1023"]}]},{"name":"RICORS2040 (Kidney Disease)","award":["RD16\/0009\/0017"],"award-info":[{"award-number":["RD16\/0009\/0017"]}]},{"name":"RICORS2040 (Kidney Disease)","award":["RD21\/0005\/0019"],"award-info":[{"award-number":["RD21\/0005\/0019"]}]},{"name":"RICORS2040 (Kidney Disease)","award":["PI17\/00384"],"award-info":[{"award-number":["PI17\/00384"]}]},{"name":"RICORS2040 (Kidney Disease)","award":["PI19\/00532"],"award-info":[{"award-number":["PI19\/00532"]}]},{"name":"RICORS2040 (Kidney Disease)","award":["PI20\/00753"],"award-info":[{"award-number":["PI20\/00753"]}]},{"name":"RICORS2040 (Kidney Disease)","award":["PI20\/00633"],"award-info":[{"award-number":["PI20\/00633"]}]},{"name":"RICORS2040 (Kidney Disease)","award":["BP19-057"],"award-info":[{"award-number":["BP19-057"]}]},{"name":"RICORS2040 (Kidney Disease)","award":["BP20-081"],"award-info":[{"award-number":["BP20-081"]}]},{"name":"RICORS2040 (Kidney Disease)","award":["FPU2019-00483"],"award-info":[{"award-number":["FPU2019-00483"]}]},{"name":"IDI-2018-000152 and IDI-2021-000080","award":["GRUPIN 14-028"],"award-info":[{"award-number":["GRUPIN 14-028"]}]},{"name":"IDI-2018-000152 and IDI-2021-000080","award":["IDI-2018-000-152"],"award-info":[{"award-number":["IDI-2018-000-152"]}]},{"name":"IDI-2018-000152 and IDI-2021-000080","award":["IDI\/2021\/000080"],"award-info":[{"award-number":["IDI\/2021\/000080"]}]},{"name":"IDI-2018-000152 and IDI-2021-000080","award":["RD12\/0021\/1023"],"award-info":[{"award-number":["RD12\/0021\/1023"]}]},{"name":"IDI-2018-000152 and IDI-2021-000080","award":["RD16\/0009\/0017"],"award-info":[{"award-number":["RD16\/0009\/0017"]}]},{"name":"IDI-2018-000152 and IDI-2021-000080","award":["RD21\/0005\/0019"],"award-info":[{"award-number":["RD21\/0005\/0019"]}]},{"name":"IDI-2018-000152 and IDI-2021-000080","award":["PI17\/00384"],"award-info":[{"award-number":["PI17\/00384"]}]},{"name":"IDI-2018-000152 and IDI-2021-000080","award":["PI19\/00532"],"award-info":[{"award-number":["PI19\/00532"]}]},{"name":"IDI-2018-000152 and IDI-2021-000080","award":["PI20\/00753"],"award-info":[{"award-number":["PI20\/00753"]}]},{"name":"IDI-2018-000152 and IDI-2021-000080","award":["PI20\/00633"],"award-info":[{"award-number":["PI20\/00633"]}]},{"name":"IDI-2018-000152 and IDI-2021-000080","award":["BP19-057"],"award-info":[{"award-number":["BP19-057"]}]},{"name":"IDI-2018-000152 and IDI-2021-000080","award":["BP20-081"],"award-info":[{"award-number":["BP20-081"]}]},{"name":"IDI-2018-000152 and IDI-2021-000080","award":["FPU2019-00483"],"award-info":[{"award-number":["FPU2019-00483"]}]},{"name":"Fundaci\u00f3n para la Investigaci\u00f3n Biosanitaria de Asturias (FINBA)","award":["GRUPIN 14-028"],"award-info":[{"award-number":["GRUPIN 14-028"]}]},{"name":"Fundaci\u00f3n para la Investigaci\u00f3n Biosanitaria de Asturias (FINBA)","award":["IDI-2018-000-152"],"award-info":[{"award-number":["IDI-2018-000-152"]}]},{"name":"Fundaci\u00f3n para la Investigaci\u00f3n Biosanitaria de Asturias (FINBA)","award":["IDI\/2021\/000080"],"award-info":[{"award-number":["IDI\/2021\/000080"]}]},{"name":"Fundaci\u00f3n para la Investigaci\u00f3n Biosanitaria de Asturias (FINBA)","award":["RD12\/0021\/1023"],"award-info":[{"award-number":["RD12\/0021\/1023"]}]},{"name":"Fundaci\u00f3n para la Investigaci\u00f3n Biosanitaria de Asturias (FINBA)","award":["RD16\/0009\/0017"],"award-info":[{"award-number":["RD16\/0009\/0017"]}]},{"name":"Fundaci\u00f3n para la Investigaci\u00f3n Biosanitaria de Asturias (FINBA)","award":["RD21\/0005\/0019"],"award-info":[{"award-number":["RD21\/0005\/0019"]}]},{"name":"Fundaci\u00f3n para la Investigaci\u00f3n Biosanitaria de Asturias (FINBA)","award":["PI17\/00384"],"award-info":[{"award-number":["PI17\/00384"]}]},{"name":"Fundaci\u00f3n para la Investigaci\u00f3n Biosanitaria de Asturias (FINBA)","award":["PI19\/00532"],"award-info":[{"award-number":["PI19\/00532"]}]},{"name":"Fundaci\u00f3n para la Investigaci\u00f3n Biosanitaria de Asturias (FINBA)","award":["PI20\/00753"],"award-info":[{"award-number":["PI20\/00753"]}]},{"name":"Fundaci\u00f3n para la Investigaci\u00f3n Biosanitaria de Asturias (FINBA)","award":["PI20\/00633"],"award-info":[{"award-number":["PI20\/00633"]}]},{"name":"Fundaci\u00f3n para la Investigaci\u00f3n Biosanitaria de Asturias (FINBA)","award":["BP19-057"],"award-info":[{"award-number":["BP19-057"]}]},{"name":"Fundaci\u00f3n para la Investigaci\u00f3n Biosanitaria de Asturias (FINBA)","award":["BP20-081"],"award-info":[{"award-number":["BP20-081"]}]},{"name":"Fundaci\u00f3n para la Investigaci\u00f3n Biosanitaria de Asturias (FINBA)","award":["FPU2019-00483"],"award-info":[{"award-number":["FPU2019-00483"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Fibrosis plays an important role in the pathogenesis of long-term diabetic complications and contributes to the development of cardiac and renal dysfunction. The aim of this experimental study, performed in a long-term rat model, which resembles type 1 diabetes mellitus, was to investigate the role of soluble Klotho (sKlotho), advanced glycation end products (AGEs)\/receptor for AGEs (RAGE), fibrotic Wnt\/\u03b2-catenin pathway, and pro-fibrotic pathways in kidney and heart. Diabetes was induced by streptozotocin. Glycaemia was maintained by insulin administration for 24 weeks. Serum and urine sKlotho, AGEs, soluble RAGE (sRAGE) and biochemical markers were studied. The levels of Klotho, RAGEs, ADAM10, markers of fibrosis (collagen deposition, fibronectin, TGF-\u03b21, and Wnt\/\u03b2-catenin pathway), hypertrophy of the kidney and\/or heart were analysed. At the end of study, diabetic rats showed higher levels of urinary sKlotho, AGEs and sRAGE and lower serum sKlotho compared with controls without differences in the renal Klotho expression. A significant positive correlation was found between urinary sKlotho and AGEs and urinary albumin\/creatinine ratio (uACR). Fibrosis and RAGE levels were significantly higher in the heart without differences in the kidney of diabetic rats compared to controls. The results also suggest the increase in sKlotho and sRAGE excretion may be due to polyuria in the diabetic rats.<\/jats:p>","DOI":"10.3390\/ijms24065241","type":"journal-article","created":{"date-parts":[[2023,3,10]],"date-time":"2023-03-10T02:30:33Z","timestamp":1678415433000},"page":"5241","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["Role of Klotho and AGE\/RAGE-Wnt\/\u03b2-Catenin Signalling Pathway on the Development of Cardiac and Renal Fibrosis in Diabetes"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1683-6617","authenticated-orcid":false,"given":"Beatriz","family":"Mart\u00edn-Carro","sequence":"first","affiliation":[{"name":"Bone and Mineral Research Unit, Instituto de Investigaci\u00f3n Sanitaria del Principado de Asturias (ISPA), Hospital Universitario Central de Asturias, 33011 Oviedo, Spain"},{"name":"Redes de Investigaci\u00f3n Cooperativa Orientadas a Resultados en Salud (RICORS), RICORS2040 (Kidney Disease), Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Mart\u00edn-V\u00edrgala","sequence":"additional","affiliation":[{"name":"Bone and Mineral Research Unit, Instituto de Investigaci\u00f3n Sanitaria del Principado de Asturias (ISPA), Hospital Universitario Central de Asturias, 33011 Oviedo, Spain"},{"name":"Redes de Investigaci\u00f3n Cooperativa Orientadas a Resultados en Salud (RICORS), RICORS2040 (Kidney Disease), Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Fern\u00e1ndez-Villabrille","sequence":"additional","affiliation":[{"name":"Bone and Mineral Research Unit, Instituto de Investigaci\u00f3n Sanitaria del Principado de Asturias (ISPA), Hospital Universitario Central de Asturias, 33011 Oviedo, Spain"},{"name":"Redes de Investigaci\u00f3n Cooperativa Orientadas a Resultados en Salud (RICORS), RICORS2040 (Kidney Disease), Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandra","family":"Fern\u00e1ndez-Fern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Laboratory of Medicine, Hospital Universitario Central de Asturias, 33011 Oviedo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8242-5365","authenticated-orcid":false,"given":"Marcos","family":"P\u00e9rez-Basterrechea","sequence":"additional","affiliation":[{"name":"Unit of Cell Therapy and Regenerative Medicine, Hematology and Hemotherapy Service, Instituto de Investigaci\u00f3n Sanitaria del Principado de Asturias (ISPA), Hospital Universitario Central de Asturias, 33011 Oviedo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5015-7474","authenticated-orcid":false,"given":"Juan F.","family":"Navarro-Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Redes de Investigaci\u00f3n Cooperativa Orientadas a Resultados en Salud (RICORS), RICORS2040 (Kidney Disease), Instituto de Salud Carlos III, 28029 Madrid, Spain"},{"name":"Research Unit, Hospital Universitario Nuestra Se\u00f1ora de Candelaria, 38010 Santa Cruz de Tenerife, Spain"},{"name":"Nephrology Service, Hospital Universitario Nuestra Se\u00f1ora de Candelaria, 38010 Santa Cruz de Tenerife, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"Donate-Correa","sequence":"additional","affiliation":[{"name":"Redes de Investigaci\u00f3n Cooperativa Orientadas a Resultados en Salud (RICORS), RICORS2040 (Kidney Disease), Instituto de Salud Carlos III, 28029 Madrid, Spain"},{"name":"Research Unit, Hospital Universitario Nuestra Se\u00f1ora de Candelaria, 38010 Santa Cruz de Tenerife, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Mora-Fern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Redes de Investigaci\u00f3n Cooperativa Orientadas a Resultados en Salud (RICORS), RICORS2040 (Kidney Disease), Instituto de Salud Carlos III, 28029 Madrid, Spain"},{"name":"Research Unit, Hospital Universitario Nuestra Se\u00f1ora de Candelaria, 38010 Santa Cruz de Tenerife, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriana S.","family":"Dusso","sequence":"additional","affiliation":[{"name":"Bone and Mineral Research Unit, Instituto de Investigaci\u00f3n Sanitaria del Principado de Asturias (ISPA), Hospital Universitario Central de Asturias, 33011 Oviedo, Spain"},{"name":"Division of Endocrinology, Metabolism and Lipid Research, Washington University School of Medicine, St. Louis, MO 63110, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4227-4144","authenticated-orcid":false,"given":"Natalia","family":"Carrillo-L\u00f3pez","sequence":"additional","affiliation":[{"name":"Bone and Mineral Research Unit, Instituto de Investigaci\u00f3n Sanitaria del Principado de Asturias (ISPA), Hospital Universitario Central de Asturias, 33011 Oviedo, Spain"},{"name":"Redes de Investigaci\u00f3n Cooperativa Orientadas a Resultados en Salud (RICORS), RICORS2040 (Kidney Disease), Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Panizo","sequence":"additional","affiliation":[{"name":"Bone and Mineral Research Unit, Instituto de Investigaci\u00f3n Sanitaria del Principado de Asturias (ISPA), Hospital Universitario Central de Asturias, 33011 Oviedo, Spain"},{"name":"Redes de Investigaci\u00f3n Cooperativa Orientadas a Resultados en Salud (RICORS), RICORS2040 (Kidney Disease), Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"Naves-D\u00edaz","sequence":"additional","affiliation":[{"name":"Bone and Mineral Research Unit, Instituto de Investigaci\u00f3n Sanitaria del Principado de Asturias (ISPA), Hospital Universitario Central de Asturias, 33011 Oviedo, Spain"},{"name":"Redes de Investigaci\u00f3n Cooperativa Orientadas a Resultados en Salud (RICORS), RICORS2040 (Kidney Disease), Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3455-1778","authenticated-orcid":false,"given":"Jos\u00e9 L.","family":"Fern\u00e1ndez-Mart\u00edn","sequence":"additional","affiliation":[{"name":"Bone and Mineral Research Unit, Instituto de Investigaci\u00f3n Sanitaria del Principado de Asturias (ISPA), Hospital Universitario Central de Asturias, 33011 Oviedo, Spain"},{"name":"Redes de Investigaci\u00f3n Cooperativa Orientadas a Resultados en Salud (RICORS), RICORS2040 (Kidney Disease), Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge B.","family":"Cannata-And\u00eda","sequence":"additional","affiliation":[{"name":"Bone and Mineral Research Unit, Instituto de Investigaci\u00f3n Sanitaria del Principado de Asturias (ISPA), Hospital Universitario Central de Asturias, 33011 Oviedo, Spain"},{"name":"Redes de Investigaci\u00f3n Cooperativa Orientadas a Resultados en Salud (RICORS), RICORS2040 (Kidney Disease), Instituto de Salud Carlos III, 28029 Madrid, Spain"},{"name":"Department of Medicine, Universidad de Oviedo, 33006 Oviedo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Alonso-Montes","sequence":"additional","affiliation":[{"name":"Bone and Mineral Research Unit, Instituto de Investigaci\u00f3n Sanitaria del Principado de Asturias (ISPA), Hospital Universitario Central de Asturias, 33011 Oviedo, Spain"},{"name":"Redes de Investigaci\u00f3n Cooperativa Orientadas a Resultados en Salud (RICORS), RICORS2040 (Kidney Disease), Instituto de Salud Carlos III, 28029 Madrid, Spain"},{"name":"Department of Psychobiology, Universidad de Oviedo, 33003 Oviedo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,9]]},"reference":[{"key":"ref_1","unstructured":"(2022, August 19). International Diabetes Federation IDF Diabetes Atlas. Available online: https:\/\/www.diabetesatlas.org\/en\/."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1607","DOI":"10.1111\/dom.14074","article-title":"Heart failure and chronic kidney disease manifestation and mortality risk associations in type 2 diabetes: A large multinational cohort study","volume":"22","author":"Birkeland","year":"2020","journal-title":"Diabetes Obes. Metab."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.2337\/dc20-2839","article-title":"Cardiovascular and Renal Disease Burden in Type 1 Compared With Type 2 Diabetes: A Two-Country Nationwide Observational Study","volume":"44","author":"Kristofi","year":"2021","journal-title":"Diabetes Care"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"695792","DOI":"10.3389\/fmed.2021.695792","article-title":"The Diabetic Cardiomyopathy: The Contributing Pathophysiological Mechanisms","volume":"8","author":"Salvatore","year":"2021","journal-title":"Front. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1007\/978-981-13-8871-2_4","article-title":"A Glimpse of the Mechanisms Related to Renal Fibrosis in Diabetic Nephropathy","volume":"1165","author":"Zeng","year":"2019","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"860","DOI":"10.4239\/wjd.v5.i6.860","article-title":"Molecular mechanisms of AGE\/RAGE-mediated fibrosis in the diabetic heart","volume":"5","author":"Zhao","year":"2014","journal-title":"World J. Diabetes"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1683","DOI":"10.2337\/db16-1281","article-title":"RAGE-Aptamer Blocks the Development and Progression of Experimental Diabetic Nephropathy","volume":"66","author":"Matsui","year":"2017","journal-title":"Diabetes"},{"key":"ref_8","first-page":"549","article-title":"Exogenous H2S mitigates myocardial fibrosis in diabetic rats through suppression of the canonical Wnt pathway","volume":"44","author":"Yang","year":"2019","journal-title":"Int. J. Mol. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1016\/j.febslet.2011.01.004","article-title":"CTGF\/CCN2 activates canonical Wnt signalling in mesangial cells through LRP6: Implications for the pathogenesis of diabetic nephropathy","volume":"585","author":"Rooney","year":"2011","journal-title":"FEBS Lett."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"101063","DOI":"10.1016\/j.arr.2020.101063","article-title":"Wnt signaling pathway in aging-related tissue fibrosis and therapies","volume":"60","author":"Hu","year":"2020","journal-title":"Ageing Res. Rev."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2169","DOI":"10.1681\/ASN.2013111209","article-title":"The kidney is the principal organ mediating klotho effects","volume":"25","author":"Lindberg","year":"2014","journal-title":"J. Am. Soc. Nephrol. JASN"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1038\/s41581-018-0078-3","article-title":"The Klotho proteins in health and disease","volume":"15","author":"Kuro","year":"2019","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.semnephrol.2012.12.013","article-title":"Renal and extrarenal actions of Klotho","volume":"33","author":"Hu","year":"2013","journal-title":"Semin. Nephrol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1104","DOI":"10.1016\/j.kint.2016.10.034","article-title":"Recombinant alpha-Klotho may be prophylactic and therapeutic for acute to chronic kidney disease progression and uremic cardiomyopathy","volume":"91","author":"Hu","year":"2017","journal-title":"Kidney Int."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1126\/science.1143578","article-title":"Augmented Wnt signaling in a mammalian model of accelerated aging","volume":"317","author":"Liu","year":"2007","journal-title":"Science"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1016\/j.kint.2018.11.021","article-title":"Wnt\/beta-catenin signaling mediates both heart and kidney injury in type 2 cardiorenal syndrome","volume":"95","author":"Zhao","year":"2019","journal-title":"Kidney Int."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"351","DOI":"10.4331\/wjbc.v6.i4.351","article-title":"Klotho in cardiovascular disease: Current and future perspectives","volume":"6","year":"2015","journal-title":"World J. Biol. Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1159\/000509369","article-title":"The Protective Role of Klotho in CKD-Associated Cardiovascular Disease","volume":"6","author":"Bi","year":"2020","journal-title":"Kidney Dis."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"F791","DOI":"10.1152\/ajprenal.00462.2017","article-title":"Klotho plays a protective role against glomerular hypertrophy in a cell cycle-dependent manner in diabetic nephropathy","volume":"315","author":"Oh","year":"2018","journal-title":"Am. J. Physiol. Ren. Physiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1016\/j.diabres.2014.08.026","article-title":"The changes of serum sKlotho and NGAL levels and their correlation in type 2 diabetes mellitus patients with different stages of urinary albumin","volume":"106","author":"Wu","year":"2014","journal-title":"Diabetes Res. Clin. Pr."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1128","DOI":"10.1136\/jim-2016-000142","article-title":"Soluble Klotho and fibroblast growth factor 23 levels in diabetic nephropathy with different stages of albuminuria","volume":"64","author":"Inci","year":"2016","journal-title":"J. Investig. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1415","DOI":"10.1016\/j.clinbiochem.2012.07.098","article-title":"Soluble serum Klotho in diabetic nephropathy: Relationship to VEGF-A","volume":"45","author":"Kacso","year":"2012","journal-title":"Clin. Biochem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"931746","DOI":"10.3389\/fphar.2022.931746","article-title":"The controversy of klotho as a potential biomarker in chronic kidney disease","volume":"13","author":"Yu","year":"2022","journal-title":"Front. Pharmacol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Typiak, M., Kulesza, T., Rachubik, P., Rogacka, D., Audzeyenka, I., Angielski, S., Saleem, M.A., and Piwkowska, A. (2021). Role of Klotho in Hyperglycemia: Its Levels and Effects on Fibroblast Growth Factor Receptors, Glycolysis, and Glomerular Filtration. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22157867"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1681\/ASN.2010010010","article-title":"Pathologic classification of diabetic nephropathy","volume":"21","author":"Tervaert","year":"2010","journal-title":"J. Am. Soc. Nephrol. JASN"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Sakan, H., Nakatani, K., Asai, O., Imura, A., Tanaka, T., Yoshimoto, S., Iwamoto, N., Kurumatani, N., Iwano, M., and Nabeshima, Y. (2014). Reduced renal alpha-Klotho expression in CKD patients and its effect on renal phosphate handling and vitamin D metabolism. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0086301"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1817","DOI":"10.2337\/dc18-0078","article-title":"Effects of Pentoxifylline on Soluble Klotho Concentrations and Renal Tubular Cell Expression in Diabetic Kidney Disease","volume":"41","author":"Ferri","year":"2018","journal-title":"Diabetes Care"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1681\/ASN.2014101030","article-title":"Renal Production, Uptake, and Handling of Circulating alphaKlotho","volume":"27","author":"Hu","year":"2016","journal-title":"J. Am. Soc. Nephrol. JASN"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2268","DOI":"10.1159\/000488172","article-title":"Klotho Reduces Necroptosis by Targeting Oxidative Stress Involved in Renal Ischemic-Reperfusion Injury","volume":"45","author":"Qian","year":"2018","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"709564","DOI":"10.3389\/fendo.2021.709564","article-title":"Soluble Klotho Is Decreased in Children With Type 1 Diabetes and Correlated With Metabolic Control","volume":"12","author":"Wikiera","year":"2021","journal-title":"Front. Endocrinol. (Lausanne)"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1002710","DOI":"10.3389\/fmolb.2022.1002710","article-title":"Endogenous advanced glycation end products in the pathogenesis of chronic diabetic complications","volume":"9","author":"Mengstie","year":"2022","journal-title":"Front. Mol. Biosci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"101958","DOI":"10.1016\/j.redox.2021.101958","article-title":"The use of the soluble receptor for advanced glycation-end products (sRAGE) as a potential biomarker of disease risk and adverse outcomes","volume":"42","author":"Erusalimsky","year":"2021","journal-title":"Redox Biol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1007\/s11010-018-3400-2","article-title":"Is there any evidence that AGE\/sRAGE is a universal biomarker\/risk marker for diseases?","volume":"451","author":"Prasad","year":"2019","journal-title":"Mol. Cell. Biochem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2756","DOI":"10.1007\/s00125-006-0394-1","article-title":"Association between serum levels of soluble receptor for advanced glycation end products and circulating advanced glycation end products in type 2 diabetes","volume":"49","author":"Tan","year":"2006","journal-title":"Diabetologia"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Tsoporis, J.N., Hatziagelaki, E., Gupta, S., Izhar, S., Salpeas, V., Tsiavou, A., Rigopoulos, A.G., Triantafyllis, A.S., Marshall, J.C., and Parker, T.G. (2020). Circulating Ligands of the Receptor for Advanced Glycation End Products and the Soluble Form of the Receptor Modulate Cardiovascular Cell Apoptosis in Diabetes. Molecules, 25.","DOI":"10.3390\/molecules25225235"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2716","DOI":"10.2337\/diacare.28.11.2716","article-title":"Decreased endogenous secretory advanced glycation end product receptor in type 1 diabetic patients: Its possible association with diabetic vascular complications","volume":"28","author":"Katakami","year":"2005","journal-title":"Diabetes Care"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1016\/j.bbagen.2016.11.040","article-title":"The shedding-derived soluble receptor for advanced glycation endproducts sustains inflammation during acute Pseudomonas aeruginosa lung infection","volume":"1861","author":"Antonelli","year":"2017","journal-title":"Biochim. Biophys. Acta\u2013Gen. Subj."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1038\/ncomms1734","article-title":"Activation of canonical Wnt signalling is required for TGF-beta-mediated fibrosis","volume":"3","author":"Akhmetshina","year":"2012","journal-title":"Nat. Commun."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"C710","DOI":"10.1152\/ajpcell.00137.2016","article-title":"sFRP2 activates Wnt\/beta-catenin signaling in cardiac fibroblasts: Differential roles in cell growth, energy metabolism, and extracellular matrix remodeling","volume":"311","author":"Lin","year":"2016","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"e017462","DOI":"10.1161\/JAHA.120.017462","article-title":"NT-proBNP by Itself Predicts Death and Cardiovascular Events in High-Risk Patients With Type 2 Diabetes Mellitus","volume":"9","author":"Malachias","year":"2020","journal-title":"J. Am. Heart Assoc."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1681\/ASN.2012080865","article-title":"Loss of Klotho contributes to kidney injury by derepression of Wnt\/beta-catenin signaling","volume":"24","author":"Zhou","year":"2013","journal-title":"J. Am. Soc. Nephrol. JASN"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1161\/CIRCRESAHA.120.317348","article-title":"Klotho Deficiency Causes Heart Aging via Impairing the Nrf2-GR Pathway","volume":"128","author":"Chen","year":"2021","journal-title":"Circ. Res."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Memmos, E., Sarafidis, P., Pateinakis, P., Tsiantoulas, A., Faitatzidou, D., Giamalis, P., Vasilikos, V., and Papagianni, A. (2019). Soluble Klotho is associated with mortality and cardiovascular events in hemodialysis. BMC Nephrol., 20.","DOI":"10.1186\/s12882-019-1391-1"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"3818196","DOI":"10.1155\/2020\/3818196","article-title":"Advanced Glycation End Products (AGEs): Biochemistry, Signaling, Analytical Methods, and Epigenetic Effects","volume":"2020","author":"Perrone","year":"2020","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_45","first-page":"223","article-title":"The demonstration of alphaKlotho deficiency in human chronic kidney disease with a novel synthetic antibody","volume":"30","author":"Barker","year":"2015","journal-title":"Nephrol. Dial. Transplant. Off. Publ. Eur. Dial. Transpl. Assoc. Eur. Ren. Assoc."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/6\/5241\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:51:47Z","timestamp":1760122307000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/6\/5241"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,9]]},"references-count":46,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2023,3]]}},"alternative-id":["ijms24065241"],"URL":"https:\/\/doi.org\/10.3390\/ijms24065241","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,9]]}}}