Integrin-linked kinase mRNA expression in circulating mononuclear cells as a biomarker of kidney and vascular damage in experimental chronic kidney disease

• Published in: Cell communication and signaling Vol. 22; no. 1; pp. 264 - 12
• Main Authors: Campillo, Sofía, Gutiérrez-Calabrés, Elena, García-Miranda, Susana, Griera, Mercedes, Fernández Rodríguez, Loreto, de Frutos, Sergio, Rodríguez-Puyol, Diego, Calleros, Laura
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 11.05.2024; BioMed Central; BMC
• Subjects: Adenine; Analysis; Animals; Aorta; Biological markers; Biomarker; Biomarkers; Biomarkers - blood; Biomarkers - metabolism; Blood circulation disorders; Cell adhesion & migration; Chronic kidney disease (CKD); Chronic kidney failure; Complications and side effects; Creatinine; Diabetes; Diet; Disease Models, Animal; Ethylenediaminetetraacetic acid; Fibrosis; Gene expression; Genetic aspects; Health aspects; Hypertension; ILK; ILK protein; Inflammation; Integrins; Kidney - metabolism; Kidney - pathology; Kidney diseases; Kinases; Leukocytes; Leukocytes (mononuclear); Leukocytes, Mononuclear - metabolism; Male; Medical research; Medicine, Experimental; Messenger RNA; Mice; Mice, Inbred C57BL; MicroRNA; MicroRNAs; MicroRNAs - blood; MicroRNAs - genetics; MicroRNAs - metabolism; Mortality; Nitrogen; Peripheral blood mononuclear cells; Physiological aspects; Plasma; Protein kinases; Protein Serine-Threonine Kinases - genetics; Protein Serine-Threonine Kinases - metabolism; Protein-serine/threonine kinase; Renal cortex; Renal damage; Renal function; Renal Insufficiency, Chronic - genetics; Renal Insufficiency, Chronic - pathology; RNA, Messenger - genetics; RNA, Messenger - metabolism; Urea; Vascular damage; Spain; United States > US; Netherlands; ILK; Biomarker; Renal damage; Vascular damage; Chronic kidney disease (CKD)
• ISSN: 1478-811X; 1478-811X
• DOI: 10.1186/s12964-024-01646-2

Traditional biomarkers of chronic kidney disease (CKD) detect the disease in its late stages and hardly predict associated vascular damage. Integrin-linked kinase (ILK) is a scaffolding protein and a serine/threonine protein kinase that plays multiple roles in several pathophysiological processes during renal damage. However, the involvement of ILK as a biomarker of CKD and its associated vascular problems remains to be fully elucidated. CKD was induced by an adenine-rich diet for 6 weeks in mice. We used an inducible ILK knockdown mice (cKD-ILK) model to decrease ILK expression. ILK content in mice's peripheral blood mononuclear cells (PBMCs) was determined and correlated with renal function parameters and with the expression of ILK and fibrosis and inflammation markers in renal and aortic tissues. Also, the expression of five miRNAs that target ILK was analyzed in whole blood of mice. The adenine diet increased ILK expression in PBMCs, renal cortex, and aortas, and creatinine and urea nitrogen concentrations in the plasma of WT mice, while these increases were not observed in cKD-ILK mice. Furthermore, ILK content in PBMCs directly correlated with renal function parameters and with the expression of renal and vascular ILK and fibrosis and inflammation markers. Finally, the expression of the five miRNAs increased in the whole blood of adenine-fed mice, although only four correlated with plasma urea nitrogen, and of those, three were downregulated in cKD-ILK mice. ILK, in circulating mononuclear cells, could be a potential biomarker of CKD and CKD-associated renal and vascular damage.