Nephropathy
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Nephropathy
Due to its rapidly increasing prevalence, chronic kidney disease (CKD) has become a global health problem. The main causes of CKD include age-related renal function decline, hypertension, diabetes, obesity as well as primary renal disorders. It has been well established that podocytes, the highly differentiated glomerular cells are critical determinants of outcome for all glomerular diseases. The limited ability of mature podocytes to self-renewal is a major cause of progressive kidney diseases, regardless of their diverse origins. Their impairment is a hallmark of glomerular diseases even at early stages. Thus, podocyte-directed therapy seems to be the most desired strategy for treatment and preventing the progression of glomerular injury.
In the past years, many studies have focused on podocyte proteins as potential therapeutic targets. Recently, an increasing number of evidence indicates that activation of autophagy could be a potent tool to prevent podocyte loss in diabetic nephropathy. On the other hand, there is a close relationship between podocyte structure and function. Recent results of studies in vitro indicate that GTPase and microRNA –mediated regulation of actin dynamics is a target in CKD. Thus, preventing changes and restoring podocyte morphology by stabilization of F-actin cytoskeleton and other structural proteins seems to be a promising approach.
Structure , function and viability of podocytes is directly regulated by various hormones, such as natriuretic peptides, angiotensin II or insulin. Recent studies emphasize a detrimental role of growth hormone in podocytes in diabetic kidney. Podocytes express also a number of nuclear hormone receptors (NR) whose ligands could serve as potential treatments in podocytopathies. While the renoprotective roles of some hormones , such as glucocorticoids or estrogens has been known for years, their direct role on podocyte function is still emerging. Further exploring the NR functions in podocyte development and disorders may shed a new light on the possibilities of a podocyte-specific therapy.
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