Tissue gene expression of renin-angiotensin system in human type 2 diabetic nephropathy

Diabetes Care. 2006 Apr;29(4):848-52. doi: 10.2337/diacare.29.04.06.dc05-1873.


Objective: Recent studies have proved that blockade of the renin-angiotensin system (RAS) retards the progression of diabetic nephropathy, whereas hyporeninemia is known as a typical state in diabetic subjects. The purpose of this study is to determine whether expression levels of RAS differ between nondiabetic and diabetic renal tissues with accurate quantitative method.

Research design and methods: Subjects were 66 nondiabetic and 8 diabetic patients with biopsy-proven renal diseases. The eight diabetic subjects suffered from type 2 diabetes with overt proteinuria. Renal histology revealed typical diffuse or nodular lesions with linear IgG deposit on immunofluorescent staining and thickened basement membrane on electronic microscopy. Total RNA from a small part of the renal cortical biopsy specimens was reverse-transcribed, and the resultant cDNA was amplified for new major components of RAS (i.e., renin, renin receptor, angiotensinogen, ACE, ACE2, angiotensin II type 1 receptor, and angiotensin II type 2 receptor) and measured.

Results: Among these components, a significant upregulation was observed in the ACE gene in diabetic renal tissue.

Conclusions: The results suggest that renal tissue RAS might be activated in the respect that ACE gene expression is upregulated in spite of a tendency to low renin expression in type 2 diabetic nephropathy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Angiotensins / genetics*
  • Angiotensins / metabolism
  • Diabetes Mellitus, Type 2 / genetics*
  • Diabetic Nephropathies / genetics*
  • Female
  • Gene Expression*
  • Glyceraldehyde-3-Phosphate Dehydrogenases / genetics
  • Glyceraldehyde-3-Phosphate Dehydrogenases / metabolism
  • Humans
  • Kidney / metabolism*
  • Kidney Diseases / genetics*
  • Kidney Diseases / metabolism
  • Male
  • Middle Aged
  • Peptidyl-Dipeptidase A / genetics
  • Peptidyl-Dipeptidase A / metabolism
  • Polymerase Chain Reaction
  • Proteinuria
  • RNA, Messenger / metabolism
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism
  • Renin / genetics
  • Renin / metabolism
  • Renin-Angiotensin System / genetics*
  • Renin-Angiotensin System / physiology
  • Up-Regulation
  • Vacuolar Proton-Translocating ATPases / genetics
  • Vacuolar Proton-Translocating ATPases / metabolism


  • ATP6AP2 protein, human
  • Angiotensins
  • RNA, Messenger
  • Receptors, Cell Surface
  • Glyceraldehyde-3-Phosphate Dehydrogenases
  • Peptidyl-Dipeptidase A
  • Renin
  • Vacuolar Proton-Translocating ATPases