Enhanced expression of ANGPTL2 in the microvascular lesions of diabetic glomerulopathy.

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. 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. 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. 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.