Nonimmunologic targets of immunosuppressive agents in podocytes
نویسندگان
چکیده
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.
منابع مشابه
The podocyte as a direct target of immunosuppressive agents.
Podocytes play a key role in maintaining the blood-urine barrier for high-molecular-weight proteins. They are considered to be terminally differentiated, and podocyte loss cannot be compensated by regenerative proliferation. Various diseases leading to podocyte damage and loss result in proteinuria and cause nephrotic syndrome. Therefore, direct therapeutical strategies to protect podocytes in ...
متن کاملPReS-FINAL-2354: Laboratory investigation of the role of toll-like receptros on kidney cells in pathogenesis of lupus nephritis
Introduction Lupus nephritis (LN) is a serious complication of juvenileonset systemic lupus erythematosus (JSLE). Current treatments include long-term immunosuppressants with significant side effects. There is a need to identify targets for more effective therapies. Toll-like receptors (TLRs) perform an important role in the innate immune response by recognising conserved molecules associated w...
متن کاملTargeting Rapamycin to Podocytes Using a Vascular Cell Adhesion Molecule-1 (VCAM-1)-Harnessed SAINT-Based Lipid Carrier System
Together with mesangial cells, glomerular endothelial cells and the basement membrane, podocytes constitute the glomerular filtration barrier (GFB) of the kidney. Podocytes play a pivotal role in the progression of various kidney-related diseases such as glomerular sclerosis and glomerulonephritis that finally lead to chronic end-stage renal disease. During podocytopathies, the slit-diaphragm c...
متن کاملCellular Effects of Everolimus and Sirolimus on Podocytes
Everolimus (EVL) and Sirolimus (SRL) are potent immunosuppressant agents belonging to the group of mammalian target of rapamycin (mTOR) inhibitors used to prevent transplant rejection. However, some patients develop proteinuria following a switch from a calcineurin inhibitor regimen to mTOR inhibitors. Whether different mTOR inhibitors show similar effects on podocytes is still unknown. To anal...
متن کامل