Loss of decay-accelerating factor triggers podocyte injury and glomerulosclerosis

Kidney glomerulosclerosis commonly progresses to end-stage kidney failure, but pathogenic mechanisms are still poorly understood. Here, we show that podocyte expression of decay-accelerating factor (DAF/CD55), a complement C3 convertase regulator, crucially controls disease in murine models of adriamycin (ADR)-induced focal and segmental glomerulosclerosis (FSGS) and streptozotocin (STZ)-induced diabetic glomerulosclerosis. ADR induces enzymatic cleavage of DAF from podocyte surfaces, leading to complement activation. C3 deficiency or prevention of C3a receptor (C3aR) signaling abrogates disease despite DAF deficiency, confirming complement dependence. Mechanistic studies show that C3a/C3aR ligations on podocytes initiate an autocrine IL-1\u3b2/IL-1R1 signaling loop that reduces nephrin expression, causing actin cytoskeleton rearrangement. Uncoupling IL-1\u3b2/IL-1R1 signaling prevents disease, providing a causal link. Glomeruli of patients with FSGS lack DAF and stain positive for C3d, and urinary C3a positively correlates with the degree of proteinuria. Together, our data indicate that the development and progression of glomerulosclerosis involve loss of podocyte DAF, triggering local, complement-dependent, IL-1\u3b2-induced podocyte injury, potentially identifying new therapeutic targets

Pediatric mastocytosis is a clonal disease associated with D816V and other activating c-Kit mutations.

International audienc

Organizational justice in sport

Research on organizational justice in sport has evolved during the past fifteen years. Much of that research has focused on the perceived fairness of equity, equality, and need when making resource distributions (distributive justice) in intercollegiate athletics. Generally, those involved with intercollegiate athletics believe resource decisions based on equality and need are the most fair, but decisions appear to be based on different principles. Scholars have also begun examining the fairness of decision-making processes (procedural justice) and the communication of those decisions (interactional justice), and how organizational justice impacts organizational outcomes, such as job satisfaction. Additionally, research has expanded to include sport settings beyond intercollegiate athletics. This article summarizes the state of research by first reviewing the general organizational justice literature to conceptually describe the constructs of interest before providing a detailed examination of sport management specific research. The paper concludes with suggestions for future research on organizational justice in sport management