Regulation of epithelial sodium channel in puromycin aminonucleoside-induced unilateral experimental nephrotic syndrome in normal and analbuminemic Nagase rats

Nephron Physiol. 2005;101(3):p51-62. doi: 10.1159/000086716. Epub 2005 Jul 12.


Background: Nephrotic syndrome (NS) is characterized by renal sodium retention and edema formation. In nephrotic rats the site of enhanced sodium retention has been localized in the cortical collecting duct (CCD). The epithelial sodium channel (ENaC) is the rate-limiting constituent of sodium transport in CCD. Amiloride, an ENaC-blocking drug, corrects the abnormal rate of sodium transport in isolated perfused CCD from puromycin aminonucleoside (PAN)-treated rats. Therefore, we hypothesized that ENaC functional expression is increased in NS.

Methods: Unilateral NS was induced by PAN in Wistar rats and analbuminemic Nagase rats (NAR). Urinary protein excretion, renal abundance of mRNA and protein of ENaC subunits, as well as the ENaC regulatory serum glucocorticoid-inducible kinase (Sgk1) and Nedd4-2, were assessed.

Results: Proteinuria appeared at day 2 in the Wistar rats and NAR. Surprisingly a downregulation rather than the expected upregulation of alpha-, beta- and gamma-ENaC mRNA abundance was observed in both Wistar rats and NAR, when the treated kidney was compared with the untreated kidney. The amount of protein of alpha-, beta- and gamma-ENaC was not affected by the NS. Sgk1 mRNA expression did not change and Nedd4-2 protein expression was only decreased at days 1 and 2 in Wistar rats.

Conclusion: ENaC mRNA and protein expression are not increased in the early phase of unilateral PAN-induced NS. Sgk1, Nedd4-2 and analbuminemia are not important regulatory factors of ENaC protein expression in experimental NS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylglucosaminidase / genetics*
  • Animals
  • Antibiotics, Antineoplastic
  • Creatine / urine
  • Endosomal Sorting Complexes Required for Transport
  • Epithelial Sodium Channels
  • Immediate-Early Proteins / genetics
  • Male
  • Nedd4 Ubiquitin Protein Ligases
  • Nephrotic Syndrome / chemically induced
  • Nephrotic Syndrome / metabolism*
  • Nephrotic Syndrome / physiopathology*
  • Protein Serine-Threonine Kinases / genetics
  • Proteinuria / chemically induced
  • Proteinuria / metabolism
  • Proteinuria / physiopathology
  • Puromycin Aminonucleoside
  • RNA, Messenger / analysis
  • Rats
  • Rats, Mutant Strains
  • Rats, Wistar
  • Serum Albumin
  • Sodium / urine
  • Sodium Channels / genetics
  • Sodium Channels / metabolism*
  • Ubiquitin-Protein Ligases / metabolism


  • Antibiotics, Antineoplastic
  • Endosomal Sorting Complexes Required for Transport
  • Epithelial Sodium Channels
  • Immediate-Early Proteins
  • RNA, Messenger
  • Serum Albumin
  • Sodium Channels
  • Puromycin Aminonucleoside
  • Sodium
  • NEDD4L protein, rat
  • Nedd4 Ubiquitin Protein Ligases
  • Nedd4 protein, rat
  • Ubiquitin-Protein Ligases
  • Protein Serine-Threonine Kinases
  • serum-glucocorticoid regulated kinase
  • Acetylglucosaminidase
  • Creatine