Abstract
Hypertensive nephrosclerosis is the second most common cause of end-stage renal disease after diabetes. For years, hypertensive kidney disease has been focused on the afferent arterioles and glomeruli damage and the involvement of the renin angiotensin system (RAS). Nonetheless, in recent years, novel evidence has demonstrated that persistent high blood pressure injures tubular cells, leading to epithelial–mesenchymal transition (EMT) and tubulointerstitial fibrosis. Injury primarily determined at the glomerular level by hypertension causes changes in post-glomerular peritubular capillaries that in turn induce endothelial damage and hypoxia. Microvasculature dysfunction, by inducing hypoxic environment, triggers inflammation, EMT with epithelial cells dedifferentiation and fibrosis. Hypertensive kidney disease also includes podocyte effacement and loss, leading to disruption of the filtration barrier. This review highlights the molecular mechanisms and histologic aspects involved in the pathophysiology of hypertensive kidney disease incorporating knowledge about EMT and tubulointerstitial fibrosis. The role of the Hsp70 chaperone on the angiotensin II–induced EMT after angiotensin II type 1 receptor (AT1R) blockage, as a possible molecular target for therapeutic strategy against hypertensive renal damage is discussed.
Highlights
Hypertension affects approximately 30% of the general population
We investigated the contributions of caveolin-1 and heat shock protein 70 (Hsp70) to the regulation of NADPH oxidase 4 (Nox4) expression in the proximal tubules of spontaneously hypertensive rats (SHR)
We demonstrated that losartan induces increased Hsp70 expression and decreased oxidative stress through Nox4 protein levels reduction in proximal tubular epithelial cells (PTECs) from SHRs
Summary
Hypertension affects approximately 30% of the general population. Hypertensive kidney disease is considered one of the consequences of long-term and poorly controlled hypertension. Molecular mechanisms and other histologic aspects have been included in the pathophysiology of hypertensive kidney disease including the injury of tubular cells that induces epithelial–mesenchymal transition (EMT) and tubulointerstitial fibrosis. Angiotensin II actively participates in renal fibrosis, in part mediated by TGFβ (transforming growth factor β) [3]. The Hsps interact in a complex network of ATPindependent and ATP-dependent chaperones that are primarily cytoprotective and are critically involved in the functional preservation of many regulatory pathways. Once their function is accomplished, the Hsps dissociate from their client proteins [8]. We provide data on the role of Hsp as a modulator of losartan effect on the cytoskeleton, intercellular junctions stabilization and the epithelial–mesenchymal transition in proximal tubular cells from an experimental model of primary hypertension
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