Expression and cellular localisation of renal endothelin-1 and endothelin receptor subtypes in autosomal-dominant polycystic kidney disease

Nephron Exp Nephrol. 2003;93(2):e80. doi: 10.1159/000068518.

Abstract

The major factors influencing the rate of progression of chronic renal disease in autosomal-dominant polycystic kidney disease (ADPKD) are unknown and there are currently no effective treatments for slowing the progression of chronic renal failure in ADPKD patients. As a first step in investigating the potential role of endothelin-1 (ET1) and its receptors (ETA and ETB) in the pathophysiology of progression in ADPKD, we have studied their expression and cellular localisation in ADPKD kidney. Immunoreactive ET1 was detected in cyst epithelia, mesangial cells and vascular smooth muscle cells suggesting continuing ET1 synthesis in the cystic kidney. Compared to healthy controls, ETA mRNA was 5-10-fold higher in ADPKD cystic kidney. In cystic kidney, neo-expression of ETA receptors was found overlying glomeruli and cysts and markedly increased in medium-sized renal arteries by microautoradiography. This is the first study to demonstrate a specific upregulation of ETA receptors in human renal disease. Future studies should address whether ETA selective antagonists may be effective in slowing renal disease progression in ADPKD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Disease Progression
  • Endothelin-1 / biosynthesis*
  • Endothelin-1 / genetics
  • Endothelin-1 / immunology
  • Female
  • Gene Expression Regulation / genetics
  • Glomerular Mesangium / blood supply
  • Glomerular Mesangium / chemistry
  • Glomerular Mesangium / pathology
  • Glomerular Mesangium / physiology
  • Humans
  • Kidney Diseases, Cystic / chemistry
  • Kidney Diseases, Cystic / pathology
  • Kidney Diseases, Cystic / surgery
  • Kidney Glomerulus / blood supply
  • Kidney Glomerulus / chemistry
  • Kidney Glomerulus / pathology
  • Kidney Glomerulus / physiology
  • Kidney Tubules / blood supply
  • Kidney Tubules / chemistry
  • Kidney Tubules / pathology
  • Kidney Tubules / physiology
  • Male
  • Middle Aged
  • Muscle, Smooth, Vascular / chemistry
  • Muscle, Smooth, Vascular / pathology
  • Muscle, Smooth, Vascular / physiology
  • Nephrectomy
  • Organ Specificity
  • Polycystic Kidney, Autosomal Dominant / chemistry
  • Polycystic Kidney, Autosomal Dominant / metabolism*
  • Polycystic Kidney, Autosomal Dominant / surgery
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Receptor, Endothelin A
  • Receptor, Endothelin B
  • Receptors, Endothelin / biosynthesis*
  • Receptors, Endothelin / genetics
  • Receptors, Endothelin / immunology

Substances

  • Endothelin-1
  • RNA, Messenger
  • Receptor, Endothelin A
  • Receptor, Endothelin B
  • Receptors, Endothelin