About this Research Topic
Technical advances in molecular and cellular biology greatly contributed to the development of new insights in the role of podocytes in kidney disease. In both, primary podocyte disease and systemic illness, podocyte injury may constitute one of the earliest events in the derangement of glomerular function, and the injurious stimuli may propagate by affecting other podocytes or neighboring cells. These insults to podocytes may induce a variety of cellular responses, including gene dysregulation, activation of oxidative stress pathways, and other reactions that lead to foot process effacement and podocyte loss, which may be counterbalanced by regeneration through differentiation of progenitor cells within the Bowman’s capsule.
More recent research has shown that abnormally elevated serum glucose and a consequent increase in cellular glucose content may lead to dysfunction in mitochondrial energy metabolism in podocytes. It has been suggested that this cellular reaction participates in the pathogenesis of glomerular diseases, especially in diabetic nephropathy.
Clinical and experimental studies have provided new perspectives on the role of lipids and lipid modulating enzymes as key determinants of podocyte function in diabetic nephropathy (DN). In both, clinical and experimental DN, renal accumulation of cholesterol correlates with the development of glomerulosclerosis. Moreover, improvement of cholesterol efflux provided by liver X receptor (LXR) agonists or cyclodextrin shows protection against DN. In addition, complex lipids, including glycerophosplipid and glycolipids, can also affect podocyte function. It has been suggested that accumulation of glycosphingolipid occurs in DN and that inhibition of glucosylceramide synthase protects from experimental DN. Furthermore, it has become clear that saturated fatty acids can negatively affect podocytes and cause ER stress, a phenomenon that is preventable by treatment with farnesoid X receptor (FXR)-activating ligands.
Recent advances in primary podocyte diseases have included the demonstration that phospholipase A2 receptor (PLA2R) is a major autoantigen in membranous nephropathy that over 30 Mendelian genes cause FSGS, and that apolipoprotein L1 (APOL1) genetic variants are a major effect susceptibility factor.
This is a propitious time for a collection of review articles that summarize recent advances in our understanding of podocyte function and dysfunction, relating to energetics, metabolism, and lipid biology, and that build upon these new insight to suggest novel therapeutic approaches.
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