• Diabetes · Sep 2014

    Angiopoietin 2 induces pericyte apoptosis via α3β1 integrin signaling in diabetic retinopathy.

    • ParkSung WookSWFight against Angiogenesis-Related Blindness Laboratory, Biomedical Research Institute, Seoul National University Hospital, Seoul, Korea Department of Biomedical Sciences, College of Medicine, Seoul National University, Seoul, Korea., Jang-Hyuk Yun, Jin Hyoung Kim, Kyu-Won Kim, Chung-Hyun Cho, and Jeong Hun Kim.
    • Fight against Angiogenesis-Related Blindness Laboratory, Biomedical Research Institute, Seoul National University Hospital, Seoul, Korea Department of Biomedical Sciences, College of Medicine, Seoul National University, Seoul, Korea.
    • Diabetes. 2014 Sep 1; 63 (9): 3057-68.

    AbstractPericyte loss is an early characteristic change in diabetic retinopathy (DR). Despite accumulating evidence that hyperglycemia-induced angiopoietin 2 (Ang2) has a central role in pericyte loss, the precise molecular mechanism has not been elucidated. This study investigated the role of Ang2 in pericyte loss in DR. We demonstrated that pericyte loss occurred with Ang2 increase in the diabetic mouse retina and that the source of Ang2 could be the endothelial cell. Ang2 induced pericyte apoptosis via the p53 pathway under high glucose, whereas Ang2 alone did not induce apoptosis. Integrin, not Tie-2 receptor, was involved for Ang2-induced pericyte apoptosis under high glucose as an Ang2 receptor. High glucose changed the integrin expression pattern, which increased integrin α3 and β1 in the pericyte. Furthermore, Ang2-induced pericyte apoptosis in vitro was effectively attenuated via p53 suppression by blocking integrin α3 and β1. Although intravitreal injection of Ang2 induced pericyte loss in C57BL/6J mice retina in vivo, intravitreal injection of anti-integrin α3 and β1 antibodies attenuated Ang2-induced pericyte loss. Taken together, Ang2 induced pericyte apoptosis under high glucose via α3β1 integrin. Glycemic control or blocking Ang2/integrin signaling could be a potential therapeutic target to prevent pericyte loss in early DR.© 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

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