Angiopoietin‐like protein 4 (ANGPTL4) is induced by high glucose in retinal pigment epithelial cells and exhibits potent angiogenic activity on retinal endothelial cells

Acta Ophthalmologica - Tập 91 Số 4 - 2013
Hirotaka Yokouchi1,2, Kohei Eto1, Wataru Nishimura1, Norio Takeda3, Yasushi Kaburagi1,4, Shuichi Yamamoto2, Kazuki Yasuda1
1Department of Metabolic Disorder, Diabetes Research Center, Research Institute, Tokyo, Japan
2Department of Ophthalmology and Visual Science, Chiba University Graduate School of Medicine, Chiba, Japan
3Department of Ophthalmology, Hospital, National Center for Global Health and Medicine, Tokyo, Japan
4Present address: Department of Diabetic Complications, Diabetes Research Center, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan.

Tóm tắt

Abstract.Purpose:  Hyperglycaemia has been identified as major risk factor for diabetic retinopathy (DR). It is widely accepted that the progression of DR is mainly due to a local imbalance of pro‐ versus anti‐angiogenic factors in the retina. In this study, we investigated whether retinal pigment epithelial (RPE) cells produced pro‐angiogenic factors under high glucose (HG) conditions in vitro.Methods:  Cultured human retinal endothelial (RE) cells were exposed to conditioned medium from retinal pigment epithelium cells (ARPE‐19) grown in HG medium and assessed for tube formation. Based on the expression profiles of ARPE‐19, we investigated whether ANGPTL4 was a major angiogenic factor released from ARPE‐19 under HG conditions using cultured human RE cells as the test system for experiments with recombinant protein, conditioned medium from ARPE‐19 and RNA interference (RNAi).Results:  The conditioned medium from ARPE‐19 cultured under HG conditions promoted tube formation of cultured human RE cells. GeneChip analysis showed that ANGPTL4 was one of the highest upregulated genes under HG conditions. In addition, recombinant ANGPTL4 promoted all of the elements of angiogenesis in human RE cells in vitro. The results of experiments using conditioned medium from ARPE‐19 combined with RNAi demonstrated that ANGPTL4 was a major angiogenic factor released from ARPE‐19 under HG conditions.Conclusions:  ANGPTL4 was induced by high glucose in RPE cells and exhibited potent angiogenic activity on RE cells. Our results are unique and may potentially add a new candidate to the long list of molecules involved in diabetic retinopathy.

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Acta Ophthalmologica

Tập 91 Số 4

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