Department of Systems Biology, Physiology Unit, Universidad de Alcalá, Alcalá de Henares, Madrid, Spain.
Fundación Renal Iñigo Álvarez de Toledo (FRIAT), Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), and RICORS2040 Kidney Disease, Instituto de Salud Carlos III, Madrid, Spain.
Cell Commun Signal. 2024 May 11;22(1):264. 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.
传统的慢性肾脏病 (CKD) 生物标志物在疾病的晚期才检测到，并且很难预测相关的血管损伤。整合素连接激酶 (ILK) 是一种支架蛋白和丝氨酸/苏氨酸蛋白激酶，在肾脏损伤过程中的多种病理生理过程中发挥多种作用。然而，ILK 作为 CKD 的生物标志物及其相关的血管问题的参与仍有待充分阐明。
通过富含腺嘌呤的饮食在小鼠中诱导 CKD 6 周。我们使用可诱导的 ILK 敲低小鼠 (cKD-ILK) 模型来降低 ILK 的表达。测定小鼠外周血单核细胞 (PBMC) 中的 ILK 含量，并将其与肾功能参数以及肾脏和主动脉组织中 ILK 及其纤维化和炎症标志物的表达相关联。此外，还分析了小鼠全血中五种靶向 ILK 的 miRNA 的表达。
腺嘌呤饮食增加了 WT 小鼠 PBMC、肾脏皮质和主动脉中 ILK 的表达，以及血浆中肌酐和尿素氮的浓度，而在 cKD-ILK 小鼠中则没有观察到这种增加。此外，PBMC 中的 ILK 含量与肾功能参数以及肾脏和血管 ILK 及其纤维化和炎症标志物的表达直接相关。最后，在腺嘌呤喂养的小鼠的全血中，五种 miRNA 的表达增加，尽管只有四种与血浆尿素氮相关，其中三种在 cKD-ILK 小鼠中下调。
循环单核细胞中的 ILK 可能是 CKD 及 CKD 相关的肾脏和血管损伤的潜在生物标志物。
