The Restrained Expression of NF-kB in Renal Tissue Ameliorates Folic Acid Induced Acute Kidney Injury in Mice

Abstract

The Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) represent family of structurally-related eukaryotic transcription factors which regulate diverse array of cellular processes including immunological responses, inflammation, apoptosis, growth & development. Increased expression of NF-kB has often been seen in many diverse diseases, suggesting the importance of genomic deregulation to disease pathophysiology. In the present study we focused on acute kidney injury (AKI), which remains one of the major risk factor showing a high rate of mortality and morbidity. The pathology associated with it, however, remains incompletely known though inflammation has been reported to be one of the major risk factor in the disease pathophysiology. The role of NF-kB thus seemed pertinent. In the present study we show that high dose of folic acid (FA) induced acute kidney injury (AKI) characterized by elevation in levels of blood urea nitrogen & serum creatinine together with extensive tubular necrosis, loss of brush border and marked reduction in mitochondria. One of the salient observations of this study was a coupled increase in the expression of renal, relA, NF-kB2, and p53 genes and proteins during folic acid induced AKI (FA AKI). Treatment of mice with NF-kB inhibitor, pyrrolidine dithio-carbamate ammonium (PDTC) lowered the expression of these transcription factors and ameliorated the aberrant renal function by decreasing serum creatinine levels. In conclusion, our results suggested that NF-kB plays a pivotal role in maintaining renal function that also involved regulating p53 levels during FA AKI.

Retracted Article: PVT1 knockdown alleviates vancomycin-induced acute kidney injury by targeting miR-124 via inactivation of NF-κB signaling

“…30 NF-kB signaling was activated in AKI models and the inhibition of NF-kB signaling ameliorated AKI. [46][47][48] Our study showed that VAN induced the activation of NF-kB signaling and the inhibition of NF-kB by PDTC lessened VAN-induced apoptosis in HK-2 cells. Moreover, PVT1 further activated NF-kB signaling in VAN-treated HK-2 cells, while this effect was weakened by increased miR-124.…”

Developmental signalling pathways in renal fibrosis: the roles of Notch, Wnt and Hedgehog

“…The increased cytokine production that accompanies fibrosis is mostly controlled by the activity of the transcription factors NF-κB and STAT. Pharmacological inhibition of NF-κB signalling by pyrrolidine dithiocarbamate significantly diminished kidney injury and ameliorated tubular degeneration, tubular necrosis and tubulointerstitial inflammation in models of kidney fibrosis induced by folate or adenine overload in mice 33,34 . Similarly, genetic deletion of STAT has been shown to ameliorate kidney fibrosis in mouse models 29,30,35 .…”

Relevance of megalin receptor injury with nuclear factor‐kappa B upregulation in acute kidney injury induced in rats

“…ROS have been conveyed to stimulate NF‐κB signaling . The oxidative stress that was revealed in the current Cd‐induced AKI rat model may account for this altitude of renal NF‐κB level . Cui et al .…”

“…level. [33] Cui et al [34] recognized the role of inflammatory transcription factors, precisely NF-B family members in pathophysiology of AKI.…”