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Advanced glycation endproducts link inflammatory cues to upregulation of galectin-1 in diabetic retinopathy
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Title: | Advanced glycation endproducts link inflammatory cues to upregulation of galectin-1 in diabetic retinopathy |
Authors: | Kanda, Atsuhiro Browse this author →KAKEN DB | Dong, Yoko Browse this author | Noda, Kousuke Browse this author →KAKEN DB | Saito, Wataru Browse this author →KAKEN DB | Ishida, Susumu Browse this author →KAKEN DB |
Issue Date: | 23-Nov-2017 |
Publisher: | Nature Publishing Group |
Journal Title: | Scientific reports |
Volume: | 7 |
Start Page: | 16168 |
Publisher DOI: | 10.1038/s41598-017-16499-8 |
Abstract: | Diabetic retinopathy (DR) is an inflammatory and progressive vaso-occlusive disease resulting in angiogenesis. Galectin-1 is a hypoxia-induced angiogenic factor associated with cancer and proliferative DR. Here we reveal a significant upregulation of galectin-1 in eyes of DR patients along with progression of clinical stages beginning from the pre-ischemic, inflammatory stage with diabetic macular edema, but not in eyes with non-diabetic retinal vascular occlusions. As for its regulatory mechanism unrelated to hypoxia but selective to DR, in vitro galectin-1/LGALS1 expression was shown to increase after application to Müller glial cells with interleukin (IL)-1β, which was induced in monocyte-derived macrophages and microglial cells via toll-like receptor (TLR) 4 signaling stimulated by advanced glycation endproducts (AGE). In vivo inhibition of AGE generation with aminoguanidine, macrophage depletion with clodronate liposomes, and antibody-based blockade of Il-1β and Tlr4 attenuated diabetes-induced retinal Lgals1 expression in mice. Fibrovascular tissues from proliferative DR eyes were immunoreactive for AGE, TRL4 and IL-1β in macrophages, and IL-1β receptor-positive glial cells expressed galectin-1. Therefore, diabetes-induced retinal AGE accumulation was suggested to activate IL-1β-related inflammatory cues in macrophages followed by Müller cells, linking to galectin-1 upregulation in human DR with time. Our data highlight AGE-triggered inflammation as the DR-selective inducer of galectin-1. |
Rights: | http://creativecommons.org/licenses/by/4.0/ |
Type: | article |
URI: | http://hdl.handle.net/2115/68213 |
Appears in Collections: | 医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 神田 敦宏
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