Expression of angiopoietin-like 3 associated with puromycin-induced podocyte damage.

Angiopoietin-like 3 (ANGPTL3) is a secreted protein of the angiopoietin family and is involved in angiogenesis and lipid metabolism regulation. However, there is little data regarding the role of ANGPTL3 in kidney injury. We recently reported the glomerular distribution of ANGPTL3 in Adriamycin nephropathy in rats. In the present paper, we report expression of ANGPTL3 by murine podocytes in vitro. Puromycin-induced injury of cultured podocytes showed a time-dependent upregulation of ANGPTL3 accompanied by a time-dependent downregulation of perlecan and agrin by Western blot and RT-PCR analysis. In addition, the increased expression of ANGPTL3 following gene transfection upregulated the expression of perlecan and agrin in podocytes. Double immunolabeling demonstrated colocalization of perlecan and ANGPTL3 on podocytes following pcDNA3.1-ANGPTL3 transfection. To explore how ANGPTL3 transfection modulates the effect of puromycin on podocytes, we compared cell adhesion in untreated podocytes and ANGPTL3-transfected podocytes. ANGPTL3 gene transfection significantly ameliorated puromycin-induced podocyte detachment. In conclusion, ANGPTL3 expression is upregulated in puromycin-induced podocyte damage and is associated with the reduction of perlecan and agrin expression. Copyright 2010 S. Karger AG, Basel.