ILK (integrin-linked kinase) is an intracellular serine/threonine kinase involved in cell-matrix interactions. ILK dysregulation has been described in chronic renal disease and modulates podocyte function and fibrosis, whereas data about its role in inflammation are scarce. AngII (angiotensin II) is a pro-inflammatory cytokine that promotes renal inflammation. AngII blockers are renoprotective and down-regulate ILK in experimental kidney disease, but the involvement of ILK in the actions of AngII in the kidney has not been addressed. Therefore we have investigated whether ILK signalling modulates the kidney response to systemic AngII infusion in wild-type and ILK-conditional knockout mice. In wild-type mice, AngII induced an inflammatory response, characterized by infiltration of monocytes/macrophages and lymphocytes, and up-regulation of pro-inflammatory factors (chemokines, adhesion molecules and cytokines). AngII activated several intracellular signalling mechanisms, such as the NF-κB (nuclear factor κB) transcription factor, Akt and production of ROS (reactive oxygen species). All these responses were prevented in AngII-infused ILK-deficient mice. In vitro studies characterized further the mechanisms regulating the inflammatory response modulated by ILK. In cultured tubular epithelial cells ILK blockade, by siRNA, inhibited AngII-induced NF-κB subunit p65 phosphorylation and its nuclear translocation. Moreover, ILK gene silencing prevented NF-κB-related pro-inflammatory gene up-regulation. The results of the present study demonstrate that ILK plays a key role in the regulation of renal inflammation by modulating the canonical NF-κB pathway, and suggest a potential therapeutic target for inflammatory renal diseases.
Integrin-linked kinase plays a key role in the regulation of angiotensin II-induced renal inflammation
Matilde Alique, Esther Civantos, Elsa Sanchez-Lopez, Carolina Lavoz, Sandra Rayego-Mateos, Raquel Rodrigues-Díez, Ana Belén García-Redondo, Jesús Egido, Alberto Ortiz, Diego Rodríguez-Puyol, Manuel Rodríguez-Puyol, Marta Ruiz-Ortega; Integrin-linked kinase plays a key role in the regulation of angiotensin II-induced renal inflammation. Clin Sci (Lond) 1 July 2014; 127 (1): 19–31. doi: https://doi.org/10.1042/CS20130412
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