NF-κB in Renal Inflammation

作者：Ana Belen Sanz, María Dolores Sánchez-Niño, Adrian Mario Ramos, Juan Antonio Moreno, Beatriz Santamaría, Marta Ruiz‐Ortega, Jesús Egido, Alberto Arduan Ortiz · 发表于：Journal of the American Society of Nephrology · 年份：2010 · DOI：10.1681/asn.2010020218 · 被引用次数：568 · 研究领域：NF-κB Signaling Pathways、Cell death mechanisms and regulation、Bone Metabolism and Diseases

The NF-kappaB family of transcription factors regulates the induction and resolution of inflammation. Two main pathways, classical and alternative, control the nuclear translocation of NF-kappaB. Classical NF-kappaB activation is usually a rapid and transient response to a wide range of stimuli whose main effector is RelA/p50. The alternative NF-kappaB pathway is a more delayed response to a smaller range of stimuli resulting in DNA binding of RelB/p52 complexes. Additional complexity in this system involves the posttranslational modification of NF-kappaB proteins and an ever-increasing range of co-activators, co-repressors, and NF-kappaB complex proteins. Collectively, NF-kappaB regulates the expression of numerous genes that play a key role in the inflammatory response during human and experimental kidney injury. Multiple stimuli activate NF-kappaB through the classical pathway in somatic renal cells, and noncanonical pathway activation by TWEAK occurs in acute kidney injury. Under most test conditions, specific NF-kappaB inhibitors tend to reduce inflammation in experimental kidney injury but not always. Although many drugs in current use clinically influence NF-kappaB activation, there are no data regarding specific NF-kappaB inhibition in human kidney disease.