Nadia Artha Dewi1, Aulanni'am Aulanni'am2, Hidayat Sujuti3, Muhammad Aris Widodo4, Djoko Wahono Soeatmadji5. 1. Department of Ophthalmology, Vitreoretinal Subdivision, Faculty of Medicine, Brawijaya University, Malang 65111, Indonesia. 2. Department of Biochemistry, Faculty of Sciences, Brawijaya University, Malang 65111, Indonesia. 3. Department of Biochemistry, Faculty of Medicine, Brawijaya University, Malang 65111, Indonesia. 4. Department of Pharmacology, Faculty of Medicine, Brawijaya University, Malang 65111, Indonesia. 5. Department of Endocrinology, Faculty of Medicine, Brawijaya University, Malang 65111, Indonesia.
Abstract
AIM: To investigate the mechanism of pericyte migration through Angiopoietin-2 (Ang-2)/Tie-2 signaling pathway. METHODS: We divided the rats into 5 groups. Each diabetic rat model groups injected with Tie-2 inhibitor, ERK1/2 inhibitor, Akt/PKB inhibitor, and DMSO intravitreal. Retinal digest preparation was done to examine the retinal vasculature including pericyte: endothelial ratio, and morphology of pericyte migration. Tie-2, ERK1/2 and Akt/PKB phosporylation were analyzed by confocal laser scanning microscopy. RESULTS: There was a correlation between pericyte migration with increasing Ang-2 (P<0.05). Pericyte number reduced by 40% (1:2.4) after 5wk diabetes on diabetic rats. The pericyte: endothelial ratio on group with Tie-2 inhibitor were 1:1.8. The same result shows on group with Akt/PKB inhibition. ERK1/2 inhibitor group shows the best results of pericyte: endothelial ratio (1:1.7). Inhibition on Tie-2 receptor decreased the phosphorylation activity of Tie-2, ERK1/2 and Akt/PKB pathway. ERK1/2 inhibition also decreasing the phosphorylation of Tie-2 and Akt/PKB. But on Akt/PKB inhibition, the phosphorylation of Tie-2 and ERK1/2 were relative the same. CONCLUSION: Ang-2 has a role for pericyte migration on diabetic rats through Tie-2 receptor, ERK1/2 and Akt/PKB pathways. ERK1/2 is a dominant pathway based on the ability to supress another pathway activity and decreasing pericyte migration on diabetic rats.
AIM: To investigate the mechanism of pericyte migration through Angiopoietin-2 (Ang-2)/Tie-2 signaling pathway. METHODS: We divided the rats into 5 groups. Each diabeticrat model groups injected with Tie-2 inhibitor, ERK1/2 inhibitor, Akt/PKB inhibitor, and DMSO intravitreal. Retinal digest preparation was done to examine the retinal vasculature including pericyte: endothelial ratio, and morphology of pericyte migration. Tie-2, ERK1/2 and Akt/PKB phosporylation were analyzed by confocal laser scanning microscopy. RESULTS: There was a correlation between pericyte migration with increasing Ang-2 (P<0.05). Pericyte number reduced by 40% (1:2.4) after 5wk diabetes on diabeticrats. The pericyte: endothelial ratio on group with Tie-2 inhibitor were 1:1.8. The same result shows on group with Akt/PKB inhibition. ERK1/2 inhibitor group shows the best results of pericyte: endothelial ratio (1:1.7). Inhibition on Tie-2 receptor decreased the phosphorylation activity of Tie-2, ERK1/2 and Akt/PKB pathway. ERK1/2 inhibition also decreasing the phosphorylation of Tie-2 and Akt/PKB. But on Akt/PKB inhibition, the phosphorylation of Tie-2 and ERK1/2 were relative the same. CONCLUSION:Ang-2 has a role for pericyte migration on diabeticrats through Tie-2 receptor, ERK1/2 and Akt/PKB pathways. ERK1/2 is a dominant pathway based on the ability to supress another pathway activity and decreasing pericyte migration on diabeticrats.
Entities:
Keywords:
Angiopoietin/Tie-2; cell migration; diabetes; pericyte; rat
Authors: Moritz Felcht; Robert Luck; Alexander Schering; Philipp Seidel; Kshitij Srivastava; Junhao Hu; Arne Bartol; Yvonne Kienast; Christiane Vettel; Elias K Loos; Simone Kutschera; Susanne Bartels; Sila Appak; Eva Besemfelder; Dorothee Terhardt; Emmanouil Chavakis; Thomas Wieland; Christian Klein; Markus Thomas; Akiyoshi Uemura; Sergij Goerdt; Hellmut G Augustin Journal: J Clin Invest Date: 2012-05-15 Impact factor: 14.808