The Role of STAT3 Activation in Glomerulonephritis

Glomerulonephritis is a renal disease characterized by inflammation of the glomeruli, i.e., small blood vessels, in the kidneys. It may present with isolated hematuria and/or proteinuria or as nephritic syndrome, acute renal failure, or chronic renal failure. Glomerulonephritis has several different pathological patterns that can be broadly grouped into non-proliferative and proliferative types. Non-proliferative types include minimal change glomerulonephritis, focal segmental glomerulosclerosis, and membranous glomerulonephritis. Proliferative types include IgA nephropathy, post-infectious glomerulonephritis, membranoproliferative/mesangiocapillary glomerulonephritis, and rapidly progressive glomerulonephritis (Miller et al., 2010). Of the many factors involved in the inflammatory response, cytokines are the most important factors that bind to their receptors and activate signal transduction pathways. Progress in our understanding of inflammatory signaling pathways has led to the identification of the involvement of nuclear factor-κB (NF-κB), mitogen-activated protein kinases (MAPKs) such as p38, and Janus tyrosine kinase-signal transducer and activator of transcription (JAK-STAT) pathways (O’Neill, 2006). The NF-κB and p38 pathways are activated by the stimulation of interleukin1 (IL-1) and tumor necrosis factor (TNF). The principal signaling pathways activated by IL-1 and TNF are the NF-κB and stress-activated MAPK pathways, whereas the JAK-STAT pathway is activated by many other cytokines.