Angiotensin II: a key factor in the inflammatory and fibrotic response in kidney diseases.
Angiotensin II (AngII) participates in the pathogenesis of renal diseases, through the regulation of two key processes inflammation and fibrosis. AT1 and AT2 are the main receptors of AngII. AT1 mediates most of the actions of AngII. This receptor regulates the expression of profibrotic factors, such as connective tissue growth factor (CTGF). The Smad signalling pathway and the Rho/Rho kinase system are two novel mechanisms involved in AngII-induced matrix regulation recently described. The role of AT2 receptors in renal pathophysiological processes is not fully elucidated. Experimental data suggest that AT2 receptors through activation of nuclear factor-kappaB participate in renal inflammatory cell recruitment. Studies in animal models of kidney injury have shown that the combined blockade of both AT1 and AT2 receptors, as well as the inhibition of the NF-kappaB pathway are necessary to stop the inflammatory process fully. On the whole, these data highlight the complex signalling systems activated by AngII and suggest novel potential targets to block fibrosis and inflammation in renal diseases.
Ruiz-Ortega
Marta
M
Vascular and Renal Research Laboratory, Fundación Jiménez Díaz, Avda. Reyes Católicos, 2, 28040 Madrid, Spain. mruizo@fjd.es
Rupérez
Mónica
M
Esteban
Vanesa
V
Rodríguez-Vita
Juan
J
Sánchez-López
Elsa
E
Carvajal
Giselle
G
Egido
Jesús
J
D000804:Angiotensin II / Q000032:analysis / Q000378:metabolism*; D016207:Cytokines / Q000032:analysis / Q000378:metabolism; D005260:Female; D005355:Fibrosis / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D018836:Inflammation Mediators / Q000032:analysis*; D007674:Kidney Diseases / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D007677:Kidney Function Tests; D008297:Male; D016328:NF-kappa B / Q000032:analysis / Q000378:metabolism*; D011379:Prognosis; D044139:Receptor, Angiotensin, Type 2 / Q000032:analysis / Q000378:metabolism*; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D015398:Signal Transduction
D016207:Cytokines; D018836:Inflammation Mediators; D016328:NF-kappa B; D044139:Receptor, Angiotensin, Type 2; D000804:Angiotensin II