A novel role of angiopoietin-like-3 associated with podocyte injury.
Article Details
- CitationCopy to clipboard
Liu J, Gao X, Zhai Y, Shen Q, Sun L, Feng C, Rao J, Liu H, Zha X, Guo M, Ma D, Zhang Z, Li R, Xu H
A novel role of angiopoietin-like-3 associated with podocyte injury.
Pediatr Res. 2015 Jun;77(6):732-9. doi: 10.1038/pr.2015.38. Epub 2015 Feb 24.
- PubMed ID
- 25710887 [ View in PubMed]
- Abstract
BACKGROUND: Angiopoietin-like-3 (ANGPTL3) expression is increased in glomerular podocytes of nephrotic syndrome. We hypothesize whether ANGPTL3 plays an important role in podocyte injury and promoting proteinuria. METHODS: Angptl3(+/+) and Angptl3(-/-) female mice on B6;129S5 gene background were injected with adriamycin by tail vein at the dose of 25 mg/Kg to produce nephropathy. Proteinuira was measured and podocytes ultrastructure was observed by electron microscopy. The interaction between ANGPTL3 and intergrin beta3 was analyzed by CO-IP and confocal immunofluorescence. The relative gene and protein expression were analyzed by RT-PCR and western blot. RESULTS: The deletion of ANGPTL3 tremendously attenuates proteinuria (more than a fivefold decrease in albuminuria) and protects podocytes from injury in a mouse model of adriamycin-induced nephropathy. We further demonstrate that ANGPTL3 interacts with and activates podocyte-expressed integrin beta3 and regulate expression of alpha-actinin-4, which may result in the cytoskeletal rearrangement of podocytes. Additionally, we identify the activation of the ANGPTL3-integrin beta3 signaling pathway in patients with nephrotic syndrome. CONCLUSION: ANGPTL3 might play a crucial role in podocyte injury. Either decreasing ANGPTL3 expression or interfering with the ANGPTL3-integrin beta3 interaction might be benefit for podocyte protection and decrease proteinuira.