NF-kappaB signalling in chronic kidney disease.
The mammalian NF-kappaB signalling pathway is an important intracellular transcription factor system that is induced in response to diverse extracellular stimuli. The hallmark of NF-kappaB activation is the nuclear translocation of dimeric Rel protein transcription factors, which regulate hundreds of kappaB-dependent genes that are involved in inflammation, immunity, apoptosis, cell proliferation and differentiation. In addition, cell-surface receptors (TNFR, Toll-like and angiotensin II, type 1 receptors), inhibitory kappaB kinases (IKK proteins), I kappaB proteins and factors regulating the post-translational modification of the Rel proteins (acetylation, phosphorylation), are other intracellular components that regulate NF-kappaB activation. Over the last decade, in vitro studies, animal models and human studies have provided evidence that upregulation of the canonical (RelA/p50) NF- kappaB isoform (in tubular epithelial cells, podocytes, mesangial cells, macrophages) has a pathogenic role in mediating chronic inflammation in chronic kidney disease (CKD). This review will examine current evidence regarding NF- kappaB isoforms and their potential role in the treatment of kidney failure due to CKD.
Rangan
Gopala
G
Centre for Transplant and Renal Research, Westmead Millennium Institute, Westmead Hospital and Sydney-West Area Health Service, Sydney, Australia. g.rangan@wmi.usyd.edu.au
Wang
Yiping
Y
Harris
David
D
D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D007676:Kidney Failure, Chronic / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D015398:Signal Transduction
D016328:NF-kappa B