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Integrin-linked kinase (ILK) regulates integrin\u2013extracellular matrix interactions and vascular integrity. This study investigated the role of ILK in CKD-associated vascular alterations. An adenine-supplemented diet induced a progressive CKD in wild-type (WT) and conditional ILK knock-down (cKD-ILK) mice. Aortic tissue was collected for histology and RT-qPCR analysis. Moreover, aortas were incubated ex vivo with the uremic toxins p-cresyl sulfate and indoxyl sulfate. In vitro, human aortic vascular smooth muscle cells were exposed to uremic toxins, and the effect of siRNA-mediated ILK silencing was tested. Aortas of adenine-fed WT mice showed a progressive increase in ILK expression, morphological alterations, and increased fibrosis, which was not observed in cKD-ILK aortas, compared to control mice. Statistically significant correlations between vascular content of ILK and fibrosis markers were observed. Ex vivo, uremic toxins increased ILK and fibrosis protein expression in WT aortas but not in cKD-ILK. In vitro, uremic toxins increased ILK activity and fibrosis markers, like collagen, while ILK-deleted cells prevented collagen increase. ILK depletion prevents CKD-associated vascular fibrosis, suggesting ILK as a potential therapeutic target to prevent arterial alterations in renal patients.<\/jats:p>","DOI":"10.3390\/ijms27010215","type":"journal-article","created":{"date-parts":[[2025,12,24]],"date-time":"2025-12-24T14:27:51Z","timestamp":1766586471000},"page":"215","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["ILK Deletion Protects Against Chronic Kidney Disease-Associated Vascular Damage"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5182-6396","authenticated-orcid":false,"given":"Sof\u00eda","family":"Campillo","sequence":"first","affiliation":[{"name":"Physiology Unit, Department of Systems Biology, Universidad de Alcal\u00e1, 28871 Alcal\u00e1 de Henares, Madrid, Spain"},{"name":"Fundaci\u00f3n Renal Espa\u00f1ola, 28003 Madrid, Spain"},{"name":"Instituto Ram\u00f3n y Cajal de Investigaci\u00f3n Sanitaria (IRYCIS), 28034 Madrid, Spain"},{"name":"INNOREN-CM, 28049 Madrid, Spain"},{"name":"RICORS 2040 RENAL, Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8144-6909","authenticated-orcid":false,"given":"Elena","family":"Guti\u00e9rrez-Calabr\u00e9s","sequence":"additional","affiliation":[{"name":"Physiology Unit, Department of Systems Biology, Universidad de Alcal\u00e1, 28871 Alcal\u00e1 de Henares, Madrid, Spain"},{"name":"Fundaci\u00f3n Renal Espa\u00f1ola, 28003 Madrid, Spain"},{"name":"Instituto Ram\u00f3n y Cajal de Investigaci\u00f3n Sanitaria (IRYCIS), 28034 Madrid, Spain"},{"name":"INNOREN-CM, 28049 Madrid, Spain"},{"name":"RICORS 2040 RENAL, Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-7364-7421","authenticated-orcid":false,"given":"Susana","family":"Garc\u00eda-Miranda","sequence":"additional","affiliation":[{"name":"Physiology Unit, Department of Systems Biology, Universidad de Alcal\u00e1, 28871 Alcal\u00e1 de Henares, Madrid, Spain"},{"name":"Fundaci\u00f3n Renal Espa\u00f1ola, 28003 Madrid, Spain"},{"name":"Instituto Ram\u00f3n y Cajal de Investigaci\u00f3n Sanitaria (IRYCIS), 28034 Madrid, Spain"},{"name":"INNOREN-CM, 28049 Madrid, Spain"},{"name":"RICORS 2040 RENAL, Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9887-6638","authenticated-orcid":false,"given":"Mercedes","family":"Griera","sequence":"additional","affiliation":[{"name":"Physiology Unit, Department of Systems Biology, Universidad de Alcal\u00e1, 28871 Alcal\u00e1 de Henares, Madrid, Spain"},{"name":"Fundaci\u00f3n Renal Espa\u00f1ola, 28003 Madrid, Spain"},{"name":"Instituto Ram\u00f3n y Cajal de Investigaci\u00f3n Sanitaria (IRYCIS), 28034 Madrid, Spain"},{"name":"INNOREN-CM, 28049 Madrid, Spain"},{"name":"RICORS 2040 RENAL, Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1225-5911","authenticated-orcid":false,"given":"Sergio","family":"de Frutos","sequence":"additional","affiliation":[{"name":"Physiology Unit, Department of Systems Biology, Universidad de Alcal\u00e1, 28871 Alcal\u00e1 de Henares, Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9125-9311","authenticated-orcid":false,"given":"Diego","family":"Rodr\u00edguez-Puyol","sequence":"additional","affiliation":[{"name":"Fundaci\u00f3n Renal Espa\u00f1ola, 28003 Madrid, Spain"},{"name":"Instituto Ram\u00f3n y Cajal de Investigaci\u00f3n Sanitaria 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Spain"},{"name":"RICORS 2040 RENAL, Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,24]]},"reference":[{"key":"ref_1","unstructured":"National Kidney Foundation (2002). 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