Nonimmunologic targets of immunosuppressive agents in podocytes

Abstract

Proteinuria is a characteristic finding in glomerular diseases and is closely associated with renal outcomes. In addition, therapeutic interventions that reduce proteinuria improve renal prognosis. Accumulating evidence has demonstrated that podocytes act as key modulators of glomerular injury and proteinuria. The podocyte, or glomerular visceral epithelial cell, is a highly specialized and differentiated cell that forms interdigitated foot processes with neighboring podocytes, which are bridged together by an extracellular structure known as the “slit diaphragm” (SD). The SD acts as a size- and charge-selective barrier to plasma protein. Derangement of SD structure or loss of SD-associated protein results in podocyte injury and proteinuria. During the past decades, several immune-modulating agents have been used for the treatment of glomerular diseases and for the reduction of proteinuria. Interestingly, recent studies have demonstrated that immunosuppressive agents can have a direct effect on the SD-associated proteins and stabilize actin cytoskeleton in podocyte and have therefore introduced the concept of nonimmunologic mechanism of renoprotection by immunomodulators. This review focuses on the evidence that immuno-modulating agents directly target podocytes.

Melanocortin 1 receptor agonist protects podocytes through catalase and RhoA activation

“…Hallmarks of podocyte injury include actin cytoskeleton rearrangement, foot process effacement, loss of slit diaphragm structures, and dedifferentiation of the podocytes (41). Treatment of patients with idiopathic membranous nephropathy (MN) with drugs such as glucocorticoids and calcineurin inhibitors can restore both structure and function, suggesting that the podocyte foot process arrangement is highly dynamic (14,44,50,63).…”

Diethylcarbamazine (DEC) in Relapse Cases of Nephrotic Syndrome in Filarial Endemic Region: A Case Series

“…Case E .6yr Male -1 st Relapse leucopenia, rash, seizures limit its use in nephrotic syndrome [7]. Levamisole attenuates podocyte apoptosis and increase in RhoA (ras homolog family member A) activity and decrease in degradation of synaptopodin protein, and so prolonging podocyte survival [8].…”

Characterization of the myoepithelial cells in the major salivary glands of the fruit bat Artibeus jamaicensis

“…). However, an increase in desmin expression in podocytes has also been related to renal diseases (Yoo & Fornoni, ). The relationship between salivary gland secretion and desmin expression is a relevant and interesting topic for further investigation.…”

“…These phenomena could be the result of either the need for more strength in these tubules or because MECs participate in ion exchange, which is one of the reported functions of the striated ducts (Bungaard et al 1977), as in case of the podocytes in the glomerulus, in which the desmin content was found to increase as rats aged (Yaoita et al 1990). However, an increase in desmin expression in podocytes has also been related to renal diseases (Yoo & Fornoni, 2015). The relationship between salivary gland secretion and desmin expression is a relevant and interesting topic for further investigation.…”