The NF-κB1 is a key regulator of acute but not chronic renal injury

Abstract

The NF-κB family of transcription factors is important for many cellular functions, in particular initiation and propagation of inflammatory and immune responses. However, recent data has suggested that different subunits of the NF-κB family can suppress the inflammatory response. NF-κB1, from the locus nfκb1, can inhibit transcription, acting as a brake to the recognised pro-inflammatory activity of other NF-κB subunits. We tested the function of NF-κB1 in an acute (nephrotoxic serum (NTS) nephritis) and a chronic (unilateral ureteric obstruction (UUO)) model of renal injury using NF-κB1 (nfκb1−/−) knockout mice. Deficiency in NF-κB1 increased the severity of glomerular injury in NTS-induced nephritis and was associated with greater proteinuria and persistent pro-inflammatory gene expression. Induction of disease in bone marrow chimeric mice demonstrated that the absence of NF-κB1 in either bone marrow or glomerular cells increased the severity of injury. Early after UUO (day 3) there was more severe histological injury in the nfκb1−/− mice but by day 10, disease severity was equivalent in wild type and nfκb1−/− mice. In conclusion, NF-κB1 modifies acute inflammatory renal injury but does not influence chronic fibrotic injury.

Deletion of NFKB1 enhances canonical NF-κB signaling and increases macrophage and myofibroblast content during tendon healing

“…Moreover, it is well established that p105 inhibits TPL2 kinase activity, reducing phosphorylation of ERK1/2 11 , and we demonstrate increased early phosphorylation of ERK1/2 at D3 in NFKB1 KO , relative to NFKB1 WT . In contrast, Fearn et al ., demonstrated that NFKB1 KO prevented ERK1/2 phosphorylation in bone marrow derived macrophages 23 , further exhibiting the cell type-specific effects of NFKB1 KO . In the present study, we found overall increases in canonical NF-κB and early ERK1/2 activation of cells involved in tendon healing, which we hypothesize to be due to the loss of repressive p50 homodimers and uninhibited TPL2 kinase.…”

Advances in understanding the innate immune‐associated diabetic kidney disease

“…52 The NF-κBdepleted mice showed increased glomerular injury, proteinuria, and inflammatory cytokine production during acute, but not chronic, renal injury. 53 Several inflammatory cytokines and chemokines such as TNF-α, IL-1, IL-6, IL-18, CCL2, and CCL5 have been found to be upregulated in kidney tissues and are associated with several renal effects, including enhanced vascular endothelial permeability, increased mesangial cell proliferation, affect extracellular matrix synthesis, and increased albuminuria. 6,[54][55][56][57][58] Studies have also suggested the implication of TNF-α in inducing the cellular apoptosis and necrosis pathways, the destabilization of the intraglomerular hemodynamics affecting the glomerular filtration rate, and the induction of NADPHmediated cellular oxidative stress leading to the production of ROS that eventually causes renal injury in diabetic human and mice.…”

Evaluation The Effect of The Aqueous Extract of Green Tea on Renal Toxicity Induced by-Methomyl in Experimental Animals Model تقییم تاثر المستخلص المائی للشای الاخضر علی تسمم الکلی المستحدث بواسطه المیثومایل فی حیوانات التجارب

“…The NF-κB transcription factors family found to have vital important in many functions inside cells, like initiation and propagation of inflammatory and immune responses (Fearn et al, 2017). Previous studies found that NF-κB has important role in the pathogenesis of renal inflammation caused by infection, injury, or autoimmune factors (Zhang andSun, 2015, Song et al, 2019).…”