Citation:Dewi NA,Aulanni’am A,Sujuti H,Widodo MA,Soeatmadji DW.Mechanism of retinal pericyte migration through Angiopoietin/Tie-2 signaling pathway on diabetic rats.Int J Ophthalmol 2018;11(3):375-381,doi:10.18240/ijo.2018.03.05
Mechanism of retinal pericyte migration through Angiopoietin/Tie-2 signaling pathway on diabetic rats
Received:June 18, 2017  Revised:January 23, 2018
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DOI:10.18240/ijo.2018.03.05
Key Words:pericyte; Angiopoietin/Tie-2; diabetes; cell migration; rat
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Nadia Artha Dewi Department of Ophthalmology, Vitreoretinal Subdivision, Faculty of Medicine, Brawijaya University, Malang 65111, Indonesia
Aulanni'am Aulanni’am Department of Biochemistry, Faculty of Sciences, Brawijaya University, Malang 65111, Indonesia
Hidayat Sujuti Department of Biochemistry, Faculty of Medicine, Brawijaya University, Malang 65111, Indonesia
Muhammad Aris Widodo Department of Pharmacology, Faculty of Medicine, Brawijaya University, Malang 65111, Indonesia
Djoko Wahono Soeatmadji Department of Endocrinology, Faculty of Medicine, Brawijaya University, Malang 65111, Indonesia
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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.

PMC FullText Html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5861225/
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