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- W2801889544 abstract "Diabetic retinopathy is considered a low-grade chronic inflammatory disease and several inflammatory molecules, including tumor necrosis factor (TNF)-α, are known to play a major role in the degeneration of retinal capillaries. Previous studies have reported that sitagliptin, a DPP-4 inhibitor, prevents the increase in blood-retinal barrier (BRB) permeability and inhibits the tight junction disassembly induced by diabetes. Our goal was to investigate whether sitagliptin is able to prevent retinal endothelial cells (EC) dysfunction triggered by the pro-inflammatory cytokine TNF-α. The effects of TNF-α and/or sitagliptin on primary cultures of bovine retinal EC were tested. The EC monolayer permeability was analyzed by using 70 kDa rhodamine isothiocyanate (RITC) dextran. The cellular distribution profile of claudin-5 was examined by immunofluorescence staining, and DPP-4 activity was evaluated by using a fluorogenic substrate. Cell viability was assessed by MTT assay, and cell proliferation by the BrdU incorporation assay. Retinal EC migration and angiogenesis were evaluated by a scratch assay and a capillary tube formation in matrigel assay, respectively. TNF-α increased the permeability of EC monolayer and induced the loss of claudin-5 immunostaining at the cell borders. This impairment was associated with decreased migration and capillary morphogenesis of retinal EC. Sitagliptin was unable to prevent the effect of TNF-α on EC permeability. However, it decreased DPP-4 activity in bovine retinal EC exposed to TNF-α, without affecting cell viability. Moreover, sitagliptin enhanced the migration and capillary morphogenesis in bovine retinal EC challenged with TNF-α. These results suggest that sitagliptin is able to positively modulate vascular EC function under conditions of retinal inflammation." @default.
- W2801889544 created "2018-05-17" @default.
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- W2801889544 date "2018-06-01" @default.
- W2801889544 modified "2023-10-18" @default.
- W2801889544 title "The dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin ameliorates retinal endothelial cell dysfunction triggered by inflammation" @default.
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- W2801889544 doi "https://doi.org/10.1016/j.biopha.2018.03.144" @default.
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