Enhanced expression of ANGPTL2 in the microvascular lesions of diabetic glomerulopathy

Nephron Exp Nephrol. 2007;105(4):e117-23. doi: 10.1159/000100493. Epub 2007 Mar 7.

Abstract

Background: Diabetic nephropathy (DN) is one of the most important microvascular complications of diabetes mellitus. However, the underlying mechanisms remain unclear. We studied the expression characteristics of angiopoietin-like 2 (ANGPTL2), a novel DN-associated growth factor identified in our previous gene chip screening.

Methods: Glomeruli were microdissected from renal biopsies from 24 patients with DN and 8 donor controls. The expression of ANGPTL2 was assessed by RT-PCR and immunohistochemistry, and then correlated with clinical and pathological indices of glomerular injury.

Results: Consistent with the results of the gene chip experiment, abundant expression of ANGPTL2 was found more frequently in diabetic glomeruli as compared to donor controls (95 vs. 38%, chi(2) = 15.9, p < 0.01). ANGPTL2 mRNA upregulation was more prominent in glomeruli with less microaneurysm (22 vs. 66%, p < 0.05), inflammatory influx (6 vs. 50%, p < 0.05) or endothelial foam cell formation (11 vs. 53%, p < 0.05). Immunostaining revealed an upregulation of ANGPTL2 protein in hypertrophied diabetic glomeruli, mainly distributed in podocytes, which were supposed to be the origin of ANGPTL2.

Conclusion: The upregulation of ANGPTL2 in diabetic glomerulopathy shows a close relationship to abnormal microvasculature and endothelial inflammation. ANGPTL2 may play an important role in the pathogenesis of diabetic glomerulopathy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiopoietin-Like Protein 2
  • Angiopoietin-like Proteins
  • Angiopoietins
  • Diabetic Nephropathies / genetics*
  • Diabetic Nephropathies / metabolism*
  • Female
  • Gene Expression Profiling
  • Genetic Predisposition to Disease / genetics
  • Humans
  • In Vitro Techniques
  • Intercellular Signaling Peptides and Proteins / genetics*
  • Intercellular Signaling Peptides and Proteins / metabolism*
  • Kidney Glomerulus / blood supply*
  • Kidney Glomerulus / metabolism*
  • Male
  • Microcirculation / metabolism*
  • Middle Aged

Substances

  • ANGPTL2 protein, human
  • Angiopoietin-Like Protein 2
  • Angiopoietin-like Proteins
  • Angiopoietins
  • Intercellular Signaling Peptides and Proteins