title: Chronic inhibition of nuclear factor kappa B attenuates aldosterone/salt-induced renal injury.
abstract: OBJECTIVE
  Recent studies suggested that nuclear factor kappa B (NF-κB) plays a key role in the pathogenesis of renal injury. This study investigated whether NF-κB inhibition attenuates progressive renal damage in aldosterone/salt-induced renal injury and its mechanisms.
  
  
  METHODS
  Adult male rats were uninephrectomized and treated with one of the following for 4 weeks: vehicle (0.5% ethanol, subcutaneously); vehicle/1% NaCl (1% NaCl in drinking solution); aldosterone/1% NaCl (1% NaCl in drinking solution and aldosterone, 0.75 μg/h, subcutaneously); or aldosterone/1%NaCl+pyrrolidine dithiocarbamate (PDTC), an inhibitor of NF-κB (100 mg/kg/day, by gavage). The activity of NF-κB was measured by EMSA and immunohistochemistry, CTGF and ICAM-1 were measured by Western blot and real-time PCR, and TGF-β and CTGF were measured by immunohistochemistry.
  
  
  RESULTS
  Rats that received aldosterone/1% NaCl exhibited hypertension and severe renal injury. Renal cortical mRNA levels of CTGF, TGF-β, ICAM-1 and collagen IV, protein expression of CTGF and ICAM-1, and NF-κB-DNA binding activity were significantly upregulated in rats that received aldosterone/1% NaCl. Treatment with PDTC significantly decreased the percentage of cells positive for CTGF and TGF-β; mRNA levels of CTGF, TGF-β, ICAM-1 and collagen IV, and protein levels of CTGF and ICAM-1 were also inhibited by PDTC.
  
  
  CONCLUSIONS
  These data suggest that the NF-κB signal pathway plays a role in the progression of aldosterone/salt-induced renal injury.
authors.affiliation: Division of Nephrology, Huashan Hospital and Institute of Nephrology, Fudan University, 12 Wulumuqi Road, Shanghai 200040, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Ding
authors.forename: Lei
authors.initials: L
authors.lastname: Yang
authors.forename: Minmin
authors.initials: M
authors.lastname: Zhang
authors.forename: Yong
authors.initials: Y
authors.lastname: Gu
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced / Q000517:prevention & control*; D000450:Aldosterone / Q000633:toxicity; D000704:Analysis of Variance; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D015153:Blotting, Western; D001835:Body Weight; D017931:DNA Primers / Q000235:genetics; D024202:Electrophoretic Mobility Shift Assay; D007150:Immunohistochemistry; D008297:Male; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D009392:Nephrectomy; D011392:Proline / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D012965:Sodium Chloride / Q000633:toxicity; D013859:Thiocarbamates / Q000494:pharmacology
chemical_list: D017931:DNA Primers; D016328:NF-kappa B; D013859:Thiocarbamates; C066229:prolinedithiocarbamate; D012965:Sodium Chloride; D000450:Aldosterone; D011392:Proline