The role of the Janus kinase family/signal transducer and activator of transcription signaling pathway in fibrotic renal disease

Abstract

Over the past several years, a number of cytokines and growth factors including transforming growth factor β1, tumor necrosis factor α, and angiotensin II have been shown to play a crucial role in renal fibrosis. The Janus kinase family (JAK) and signal transducers and activators of transcription (STATs) constitute one of the primary signaling pathways that regulate cytokine expression, and the JAK/STAT signaling pathway has increasingly been implicated in the pathophysiology of renal disease. This review examines the role of the JAK/STAT signaling pathway in fibrotic renal disease. The JAK/STAT signaling pathway is activated in a variety of renal diseases and has been implicated in the pathophysiology of renal fibrosis. Experimental evidence suggests that inhibition of the JAK/STAT signaling pathway, in particular JAK2 and STAT3, may suppress renal fibrosis and protect renal function. However, it is incompletely understood which cells activate the JAK/STAT signaling pathway and which JAK/STAT signaling pathway is activated in each renal disease. Research regarding JAK/STAT signaling and its contribution to renal disease is still ongoing in humans. Future studies are required to elucidate the potential role of JAK/STAT signaling inhibition as a therapeutic strategy in the attenuation of renal fibrosis.

Fig. 1

The JAK/STAT signaling pathway. After cytokine binding to the cytokine receptor, JAK becomes activated and phosphorylates tyrosine residues of the cytokine receptor to create docking sites for STAT. After STAT phosphorylation and activation, STATs form dimers and translocate into the nucleus where they activate the transcription of target genes. STATs are negatively regulated by several mechanisms such as SOCS and PIAS. SOCS = suppressors of cytokine signaling; PIAS = protein inhibitors of activated STAT. (Color version of figure is available online.)