| First Author | Liu J | Year | 2015 |
| Journal | Pediatr Res | Volume | 77 |
| Issue | 6 | Pages | 732-9 |
| PubMed ID | 25710887 | Mgi Jnum | J:244720 |
| Mgi Id | MGI:5913499 | Doi | 10.1038/pr.2015.38 |
| Citation | Liu J, et al. (2015) A novel role of angiopoietin-like-3 associated with podocyte injury. Pediatr Res 77(6):732-9 |
| abstractText | 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. |
