Chronic inhibition of nuclear factor-κB attenuates renal injury in the 5/6 renal ablation model

Fujihara, Clarice Kazue; Antunes, G. R.; Mattar, Ana Lucia; Malheiros, Denise Maria Avancini Costa; Vieira, J.M.; Zatz, Roberto

doi:10.1152/ajprenal.00184.2006

Cited by 121 publications

(118 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The increasing awareness of NF-B diversity in terms of regulatory components and actions calls for more detailed preclinical studies to pinpoint the timeframe and optimal target for potential clinical therapy. 79 Decreased proteinuria Diabetic nephropathy 80 Decreased inflammation AKI, sepsis 39 Decreased inflammation AKI; zymosan 81 Decreased inflammation 5/6 renal ablation model 82 Decreased inflammation AngII-infused renal injury 54,83 Decreased inflammation Parthenolide Glomerulonephritis 56 Decreased inflammation, proteinuria AKI; cisplatin 87 Decreased inflammation, proteinuria AngII-induced kidney injury 67 Decreased inflammation gliotoxin Glomerulonephritis 56 Decreased inflammation, proteinuria DHMEQ Glomerulonephritis 88 Decreased inflammation, proteinuria Specific approaches decoy B ODN Glomerulonephritis, crescentic 90 Decreased inflammation Allogenic renal transplant 92 Decreased inflammation AKI, ischemia-reperfusion 89 Decreased inflammation UUO 91 Decreased inflammation p50 siRNA AKI, sepsis 39 Improved renal function, decreased inflammation p50 knockout AKI, endotoxemia 40 Prolonged inflammation, increased mortality IB␣ super-repressor Protein overload proteinuria 93 Decreased inflammation DHMEQ, dehydroxymethyl-epoxyquinomicin; ODN, oligodeoxynucleotides; PDTC, pyrrolidinedithiocarbamate; siRNA, small interfering RNA; UUO, unilateral ureteral obstruction.…”

Section: Resultsmentioning

confidence: 99%

NF-κB in Renal Inflammation

Sanz¹,

Sanchez-Niño²,

Ramos³

et al. 2010

Journal of the American Society of Nephrology

505

379

View full text Add to dashboard Cite

Section: Resultsmentioning

confidence: 99%

NF-κB in Renal Inflammation

Sanz¹,

Sanchez-Niño²,

Ramos³

et al. 2010

Journal of the American Society of Nephrology

505

379

View full text Add to dashboard Cite

“…15 Inhibition of renal inflammation by different maneuvers is therapeutically effective, resulting in an amelioration of renal fibrotic lesions in various experimental animal models. 16,17 Several lines of evidence have suggested a potential antiinflammatory activity of vitamin D in CKD. 6,18 In animal models of primary glomerular diseases, administration of vitamin D reduces glomerular infiltration of inflammatory cells.…”

mentioning

confidence: 99%

Paricalcitol Inhibits Renal Inflammation by Promoting Vitamin D Receptor–Mediated Sequestration of NF-κB Signaling

Tan

Wen

Liu

2008

Journal of the American Society of Nephrology

243

194

View full text Add to dashboard Cite

Inflammation is a pathologic feature of a variety of chronic kidney diseases. Several lines of evidence suggest a potential anti-inflammatory role for vitamin D in chronic kidney disease, but the underlying mechanism remains unknown. Here, the effect of the synthetic vitamin D analogue paricalcitol on renal inflammation was investigated in a mouse model of obstructive nephropathy. Paricalcitol reduced infiltration of T cells and macrophages in the obstructed kidney. This inhibition of inflammatory cell infiltration was accompanied by a decreased expression of RANTES and TNF-␣. Induction of RANTES was localized primarily to the tubular epithelium, underscoring a role for tubular cells in renal inflammation. In a human proximal tubular cell line (HKC-8), paricalcitol inhibited RANTES mRNA and protein expression and abolished the ability of tubular cells to recruit lymphocytes and monocytes after TNF-␣ stimulation. Although RANTES induction depended on NF-B signaling, paricalcitol affected neither TNF-␣-mediated IB␣ phosphorylation and degradation nor p65 NF-B activation and nuclear translocation. Instead, chromatin immunoprecipitation assay showed that paricalcitol abolished the binding of p65 to its cognate cis-acting element in the RANTES promoter. The vitamin D receptor (VDR) and p65 formed a complex in tubular cells after paricalcitol treatment, which inhibited the ability of p65 to trans-activate gene transcription. In vivo, paricalcitol did not block NF-B nuclear translocation after obstructive injury but did increase the expression and nuclear distribution of VDR. These results suggest that paricalcitol inhibits renal inflammatory infiltration and RANTES expression by promoting VDRmediated sequestration of NF-B signaling.

show abstract

“…PDTC had been used in a previous study of adult rats, and found to be effective by the oral route. 12 In preliminary experiments with lactating rats, PDTC was also shown to be effective by this route, and the dose of 280 mg kg -1 day -1 was found to be the highest dose not causing death or severe growth retardation of dams or pups. After weaning, male rats were kept in cages in groups of no more than four, receiving ad libitum food and water.…”

Section: Experimental Groupsmentioning

confidence: 97%

“…[8][9][10][11] Accordingly, continuous inhibition of this system exerts a protective effect in an experimental model of chronic kidney disease. 12 However, it is presently unknown whether the NF-kB system participates in organogenesis and, particularly, whether blockade of this system during nephrogenesis would lead to changes similar to those observed with administration of RAS suppressors.…”

Section: Introductionmentioning

confidence: 99%

Programmed hypertension in rats treated with a NF-κB inhibitor during nephrogenesis: renal mechanisms

et al. 2011

Self Cite

View full text Add to dashboard Cite

Suppression of the renin-angiotensin system (RAS) during murine lactation causes progressive renal injury, indicating a physiological action of angiotensin II on nephrogenesis. The nuclear factor NF-jB system is one of the main intracellular mediators of angiotensin II. We investigated whether inhibition of this system with pyrrolidine dithiocarbamate (PDTC) during rat nephrogenesis would lead to similar hypertension and renal injury as observed with RAS suppressors. Immediately after delivery, 32 Munich-Wistar dams, each nursing 6 male pups, were divided into 2 groups: C, untreated, and PDTC, receiving PDTC, 280 mg kg -1 day -1 orally, during 21 days. After weaning, the offspring were followed until 10 months of age without treatment. Adult rats that received neonatal PDTC exhibited stable hypertension and myocardial injury, without albuminuria. To gain additional insight into this process, the renal expression of RAS components and sodium transporters were determined by quantitative real-time PCR (qRT-PCR) at 3 and 10 months of life. Renal renin and angiotensinogen were upregulated at 3 and downregulated at 10 months of age, suggesting a role for early local RAS activation. Likewise, there was early upregulation of the proximal sodium/glucose and sodium/bicarbonate transporters, which abated later in life, suggesting that additional factors sustained hypertension in the long run. The conclusions drawn from the findings were as follows: (1) an intact NF-jB system during nephrogenesis may be essential to normal renal and cardiovascular function in adult life; (2) neonatal PDTC represents a new model of hypertension, lacking overt structural injury or functional impairment of the kidneys; and (3) hypertension in this model seems associated with early temporary activation of renal RAS and sodium transporters.

show abstract

Chronic inhibition of nuclear factor-κB attenuates renal injury in the 5/6 renal ablation model

Abstract: Fujihara CK, Antunes GR, Mattar AL, Malheiros DMAC, Vieira JM Jr, Zatz R. Chronic inhibition of nuclear factor-B attenuates renal injury in the 5/6 renal ablation model. Am J Physiol

Cited by 121 publications

References 40 publications

NF-κB in Renal Inflammation

NF-κB in Renal Inflammation

Paricalcitol Inhibits Renal Inflammation by Promoting Vitamin D Receptor–Mediated Sequestration of NF-κB Signaling

Programmed hypertension in rats treated with a NF-κB inhibitor during nephrogenesis: renal mechanisms

Contact Info

Product

Resources

About