Angiotensin II Induces Expression of the Tie2 Receptor Ligand, Angiopoietin-2, in Bovine Retinal Endothelial Cells
- Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Kyoto, Japan
Abstract
Recent studies have shown that angiopoietins (Angs) and their receptor, Tie2, play a role in vascular integrity and neovascularization. The renin-angiotensin system has been hypothesized to contribute to the development of diabetic retinopathy. In this study, we investigated the effect of angiotensin II (AII) on Ang1 and Ang2 expression in cultured bovine retinal endothelial cells (BRECs). AII stimulated Ang2 but not Ang1 mRNA expression in a dose- and time-dependent manner. This response was inhibited completely by angiotensin type 1 receptor (AT1) antagonist. AII increased the transcription of Ang2 mRNA, but did not change the half-life. Protein kinase C (PKC) inhibitor completely inhibited AII-induced Ang2 expression, and the mitogen-activated protein kinase (MAPK) inhibitor also inhibited it by 69.4 ± 15.6%. In addition, we confirmed the upregulation of Ang2 in an AII-induced in vivo rat corneal neovascularization model. These data suggest that AII stimulates Ang2 expression through AT1 receptor-mediated PKC and MAPK pathways in BREC, and AII may play a novel role in retinal neovascularization.
- AII, angiotensin II
- Ang, angiopoietin
- AT1, angiotensin type 1 receptor
- BAEC, bovine aortic endothelial cell
- BREC, bovine retinal endothelial cell
- BRP, bovine retinal pericyte
- DMEM, Dulbecco’s modified Eagle’s medium
- MAPK, mitogen-activated protein kinase
- PCR, polymerase chain reaction
- PDHS, plasma-deprived horse serum
- PKC, protein kinase C
- PMA, phorbol 12-myristate 13-acetate
- RAS, renin-angiotensin system
- RTK, receptor tyrosine kinase
- VEGF, vascular endothelial growth factor
Footnotes
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Address correspondence and reprint requests to Hitoshi Takagi, Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Kyoto 606, Japan. E-mail: hitoshi{at}kuhp.kyoto-u.ac.jp.
Received for publication 22 March 2000 and accepted in revised form 4 January 2001.
