Does the AMP-activated protein kinase (AMPK) contribute to the increase of extracellular matrix induced by angiotensin II in cultured human mesangial cells? Possible role of oxidative stress via NADPH oxidase

Abstract

Chronic kidney disease (CKD) is a public health problem. In Brazil, the main causes of CKD are hypertension and diabetes mellitus. Independently of the etiology, the rule is the functional loss of the organ associated with the replacement of renal parenchyma by fibrous tissue. The activation of the renin-angiotensin aldosterone system (RAAS) is common in many renal diseases and plays a crucial role in the development of fibrosis and renal failure. Several lines of evidence suggest that AMP-activated protein kinase (AMPK) is able to confer renal protection. The aim of this project is to investigate the interaction between AMPK and the RAAS in the accumulation of extracellular matrix (ECM), a process that precedes renal fibrosis. For this, human mesangial cells will be exposed to angiotensin II (ANG II) with or without RAAS blockade, in the presence or absence of AMPK activator or blocker. The expression of ECM components will be estimated by Western blot and immunohistochemistry. The regulation of AMPK by ANG II in renal fibrosis has the potential to identify new therapies for the treatment and prevention of renal failure. (AU)