Angiopoietin-like protein 3 modulates barrier properties of human glomerular endothelial cells through a possible signaling pathway involving phosphatidylinositol-3 kinase/protein kinase B and integrin αVβ3
Article first published online: 28 JUN 2008
DOI: 10.1111/j.1745-7270.2008.00421.x
© 2008 Institute of Biochemistry and Cell Biology, SIBS, CAS
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How to Cite
Li, Y., Sun, L., Xu, H., Fang, Z., Yao, W., Guo, W., Rao, J. and Zha, X. (2008), Angiopoietin-like protein 3 modulates barrier properties of human glomerular endothelial cells through a possible signaling pathway involving phosphatidylinositol-3 kinase/protein kinase B and integrin αVβ3. Acta Biochimica et Biophysica Sinica, 40: 459–465. doi: 10.1111/j.1745-7270.2008.00421.x
Publication History
- Issue published online: 28 JUN 2008
- Article first published online: 28 JUN 2008
- Received: December 18, 2007 Accepted: April 5, 2008
- Abstract
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Keywords:
- angiopoietin-like protein 3;
- glomerular endothelial cells;
- glomerular filtration barrier;
- PI3K/Akt pathway;
- integrin αVβ3
Podocytes can influence glomerular endothelial cell (GEnC) barrier properties and take part in the development of proteinuria by some molecules. Angiopoietin-like protein 3 (Angptl3), secreted by podocytes, is a member of the angiopoietin-like protein family that has important biological functions in endothelial cells. In our previous studies, we showed that mRNA expression of Angptl3 increased significantly in kidneys of children with minimal change nephrotic syndrome. And the mRNA level of Angptl3 was increased in the glomerulus of adriamycin rats with the development of proteinuria. It was also found that Angptl3 was expressed in the cytoplasm of cultured podocytes. Thus, Angptl3 might influence the biological functions of GEnCs in a paracrine manner. In this study, we found that Angptl3 could increase the permeability of GEnCs and increase the level of protein kinase B phosphorylation in cultured GEnCs in vitro. LY294002, a phosphatidylinositol-3 kinase inhibitor, could prevent the increase of permeability of GEnCs induced by Angptl3. Our results also indicated that the integrin αVβ3 antibody (LM609) could block the Angptl3-induced protein kinase B phosphorylation.

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