Changing gears in the course of glomerulonephritis by shifting superoxide to nitric oxide-dominated chemistry.

Abstract

The glomerular response to injury displays astonishingly uniform features that include infiltration with professional immune cells, activation and proliferation of resident glomerular cells and matrix expansion. Cross-communication of intrinsic mesangial cells with invading immune cells is crucial for the fate of glomerular injury: progression to glomerulosclerosis or resolution and repair. The formation of free radicals, particularly of nitric oxide and superoxide, are key events that initiate redox-based signal transduction and gene expression. The balance between these radicals constitutes redox-operated genetic switches that ensure self-limited inflammatory responses to tissue injury. The aberrant production of the mediators, however, may sustain matrix accumulation and result in irreversible alteration of glomerular structure and function.