Downregulation of angiotensin type 1 receptor and nuclear factor-κB by sirtuin 1 contributes to renoprotection in unilateral ureteral obstruction

It has been demonstrated previously that ureteral obstruction was associated with downregulation of renal AQP2 expression and an impaired urinary concentrating capacity (Li C, Wang W, Kwon TH, Isikay L, Wen JG, Marples D, Djurhuus JC, Stockwell A, Knepper MA, Nielsen S, and Frøkiær J. Am J Physiol Renal Physiol 281: F163–F171, 2001). In the present study, changes in the expression of major renal Na transporters were examined in a rat model with 24 h of unilateral ureteral obstruction (UUO) to clarify the molecular mechanisms of the marked natriuresis seen after release of UUO. Urine collection for 2 h after release of UUO revealed a significant reduction in urinary osmolality, solute-free water reabsorption, and a marked natriuresis (0.29 ± 0.03 vs. 0.17 ± 0.03 μmol/min, P < 0.05). Consistent with this, immunoblotting revealed significant reductions in the abundance of major renal Na transporters: type 3 Na+/H+exchanger (NHE3; 24 ± 4% of sham-operated control levels), type 2 Na-Pi cotransporter (NaPi-2; 21 ± 4%), Na-K-ATPase (37 ± 4%), type 1 bumetanide-sensitive Na-K-2Cl cotransporter (BSC-1; 15 ± 3%), and thiazide-sensitive Na-Cl cotransporter (TSC; 15 ± 4%). Immunocytochemistry confirmed the downregulation of NHE3, BSC-1, and TSC in response to obstruction. In nonobstructed contralateral kidneys, a significant reduction in the abundance of inner medullary Na-K-ATPase and cortical NaPi-2 was found. This may contribute to the compensatory increase in urinary production (23 ± 2 vs. 13 ± 1 μl · min−1 · kg−1) and increased fractional excretion of urinary Na (0.62 ± 0.03 vs. 0.44 ± 0.03%, P < 0.05). In conclusion, downregulation of major renal Na transporters in rats with UUO may contribute to the impairment in urinary concentrating capacity and natriuresis after release of obstruction, and reduced levels of Na-K-ATPase and NaPi-2 in the contralateral nonobstructed kidney may contribute to the compensatory increase in water and Na excretion from that kidney during UUO and after release of obstruction.

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Osteopontin Stimulates Tumor Growth and Activation of Promatrix Metalloproteinase-2 through Nuclear Factor-κB-mediated Induction of Membrane Type 1 Matrix Metalloproteinase in Murine Melanoma Cells

Journal of Biological Chemistry ◽

10.1074/jbc.m103334200 ◽

2001 ◽

Vol 276 (48) ◽

pp. 44926-44935 ◽

Cited By ~ 179

Author(s):

Subha Philip ◽

Anuradha Bulbule ◽

Gopal C. Kundu

Keyword(s):

Matrix Metalloproteinase ◽

Tumor Growth ◽

Nuclear Factor Κb ◽

Melanoma Cells ◽

Nuclear Factor ◽

Murine Melanoma ◽

Membrane Type ◽

Murine Melanoma Cells

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Enalapril decreases nuclear factor κB activation in the kidney with ureteral obstruction: Rapid Communication

Kidney International ◽

10.1038/ki.1997.414 ◽

1997 ◽

Vol 52 (4) ◽

pp. 926-933 ◽

Cited By ~ 84

Author(s):

Jeremiah J. Morrissey ◽

Saulo Klahr

Keyword(s):

Ureteral Obstruction ◽

Nuclear Factor Κb ◽

Nuclear Factor ◽

Rapid Communication

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Differential involvement of nuclear factor-κB and activator protein-1 pathways in the interleukin-1β-mediated decrease of deiodinase type 1 and thyroid hormone receptor β1 mRNA

Journal of Endocrinology ◽

10.1677/joe.1.06354 ◽

2006 ◽

Vol 189 (1) ◽

pp. 37-44 ◽

Cited By ~ 32

Author(s):

J Kwakkel ◽

W M Wiersinga ◽

A Boelen

Keyword(s):

Thyroid Hormone ◽

Hormone Receptor ◽

Thyroid Hormone Receptor ◽

Nuclear Factor Κb ◽

Hepatoma Cell Line ◽

Nuclear Factor ◽

Activator Protein 1 ◽

Activator Protein ◽

Nfκb Pathway

One of the hallmarks of the sick euthyroid syndrome or non-thyroidal illness is a decrease of serum triiodothyronine, caused mainly by a decrease in liver deiodinase type 1 (D1) mRNA and activity. Proinflammatory cytokines like interleukin (IL)-1β are likely involved in this disease, but are also known to inhibit thyroid hormone receptor (TR)-β1 gene expression, which is of interest as the D1 promoter contains TREs. The aim of the present study was to evaluate whether the IL-1β-induced decrease of D1 and TRβ1 mRNA is mediated by the same cytokine signalling pathways in a human hepatoma cell line (HepG2). We observed a downregulation of both D1 and TRβ1 mRNA after 4 h of incubating the cells with IL-1β. Sulfasalazine was used to inhibit the nuclear factor-κB (NFκB) pathway and SP600125, a chemical inhibitor of the c-Jun N-terminal kinase, was used as an inhibitor of the activator protein-1 (AP-1) pathway. AP-1 inhibition did not affect the decrease of D1 and TRβ1 mRNA, but the TRβ1 mRNA decrease was completely abolished after inhibiting NFκB, while D1 mRNA was unaffected. Only simultaneous inhibition of both the NFκB and AP-1 pathways abolished the D1 mRNA decrease. We concluded that IL-1β stimulation of HepG2 cells results in a marked decrease of D1 and TRβ1 mRNA. The decrease of TRβ1 mRNA is exclusively mediated by the NFκB pathway, while the decrease of D1 mRNA requires inhibition of both the AP-1 and the NFκB pathways.

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