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Autophagy is a highly conserved process that degrades cellular long-lived proteins and organelles. Accumulating evidence indicates that autophagy plays a critical role in kidney maintenance, diseases and aging. Ischemic, toxic, immunological, and oxidative insults can cause an induction of autophagy in renal epithelial cells modifying the course of various(More)
The molecular mechanisms by which cyclosporine induces chronic nephrotoxicity remain poorly understood. A previous transcriptomic study suggested that cyclosporine might induce endoplasmic reticulum (ER) stress in human tubular cells. The aim of the present study was to characterize the features of tubular ER stress induced by cyclosporine and to(More)
The renal epithelium contributes to the development of inflammation during ischemic injury. Ischemia induces endoplasmic reticulum (ER) stress and activates the unfolded protein response (UPR). Ischemic tissues generate distress signals and inflammation that activates fibrogenesis and may promote adaptive immunity. Interestingly, the UPR may activate(More)
Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited renal disease, and sirolimus, a mammalian target of rapamycin (mTOR) inhibitor, has been shown to significantly retard cyst expansion in animal models. The optimal therapeutic dose of sirolimus is not yet defined. Here, we report the history of a previously unknown ADPKD(More)
In response to ischemic, toxic or immunological insults, the more frequent injuries encountered by the kidney, cells must adapt to maintain vital metabolic functions and avoid cell death. Among the adaptive responses activated, autophagy emerges as an important integrator of various extracellular and intracellular triggers (often related to nutrients(More)
Chronic allograft nephropathy accounts for the loss of approximately 40% of allografts at 10 yr. Currently, no biomarker is available to detect interstitial fibrosis and tubular atrophy in the renal graft at an early stage, when intervention may be beneficial. Because tubular epithelial cells have been shown to exhibit phenotypic changes suggestive of(More)
Sirolimus (SRL) is a recently available immunosuppressive agent. SRL, is a macrolide isolated from Streptomyces hydroscopicus that, in complex with its cellular receptor, FK binding protein, potently inhibits downstream signaling by the mammalian target of rapamycin (mTOR). It has been shown to reduce the incidence of acute rejection episode after renal(More)
Autophagy degrades pathogens, altered organelles and protein aggregates, and is characterized by the sequestration of cytoplasmic cargos within double-membrane-limited vesicles called autophagosomes. The process is regulated by inputs from the cellular microenvironment, and is activated in response to nutrient scarcity and immune triggers, which signal(More)
Retrospective studies suggest that chronic allograft nephropathy might progress more rapidly in patients with post-transplant anemia, but whether correction of anemia improves renal outcomes is unknown. An open-label, multicenter, randomized controlled trial investigated the effect of epoetin-β to normalize hemoglobin values (13.0-15.0 g/dl, n=63) compared(More)
A major side effect of the powerful immunosuppressive drug cyclosporine (CsA) is the development of a chronic nephrotoxicity whose mechanisms are not fully understood. Recent data suggest that tubular cells play a central role in the pathogenesis of chronic nephropathies. We have shown that CsA is responsible for endoplasmic reticulum (ER) stress in tubular(More)