Insight into the role of angiopoietin-like protein 4 in podocypopathies (Review).

Angiopoietin-like proteins are a group of seven proteins whose structure is different from that of angiopoietins in linkage to Tie2 or Tie1 receptors. Angiopoietin-like protein 4 (ANGPTL4), which is also known as peroxisome proliferator-activated receptor-γ (peroxisome proliferator-activated receptors-γ) angiopoietin-related or fasting-induced adipose factor, exists in two isoforms: Hyposialylated ANGPTL4 with a high-isoelectric point (high-pI), and normal sialylated ANGPTL4 with a neutral isoelectric point (neutral-pI). The present review discusses the role of ANGPTL4 in podocypopathies. Neutral-pI ANGPTL4 may also reduce proteinuria by binding β5 integrin and is secreted in various glomerulonephritis, while high-pI ANGPTL4 is upregulated in minimal change disease (MCD), modifying slight diaphragm power and increasing protein loss. In experimental animal models, high-pI ANGPTL4 is present in higher concentrations in MCD relapses than in disease remission. The administration of N-acetylmannosamine converts high-pI ANGPTL4 to neutral-pI ANGPTL4 and intraperitoneal epigallocatechin-3-gallate reduces the glomerular expression of ANGPTL4, with a reduction in albuminuria. Glomerular ANGPTL4 upregulation appears earlier in animal models, suggesting that the dysregulation of glomerular ANGPTL4 may result in foot process damage. Serum ANGPTL4 and proteinuria are likely reduced following glucocorticoid therapy. A high pI ANGPTL4/neutral pI ANGPTL4 ratios or their ratio compared to soluble urokinase-type plasminogen activator receptor could identify a marker for the differential diagnosis between early focal segmental glomerulosclerosis and MCD, in younger patients or in those who are not eligible for a kidney biopsy. [ABSTRACT FROM AUTHOR]