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The Expression Of Components Of HMGB1Signaling Pathway In Diabetic Retinopathy

Posted on:2015-02-11Degree:MasterType:Thesis
Country:ChinaCandidate:X L ChenFull Text:PDF
GTID:2284330434954734Subject:Ophthalmology
Abstract/Summary:PDF Full Text Request
Aims: Inflammation is considered to play a critical role in thepathogenesis of diabetic retinopathy, and high-mobility group box protein1(HMGB1) could promote inflammation as an alarmin. Herein, weinvestigated the expression of HMGB1signaling pathway components intype2diabetic rat retinas and in high glucose cultured ARPE-19cells,hoping to provide new research way for diabetic retinopathy.Methods: Retinal expression of HMGB1and its receptors in type2diabetic rats were detected by western blot and immunohistochemistry.ARPE-19cells were cultured with low glucose, high glucose (with orwithout anti-HMGB1antibody) or mannitol control for different time length(12,24,48,72h). Then expression of HMGB1and its receptors weremeasured by immunocytochemistry, ELISA or western blot. NF-кB activityand TNF-α/VEGF production in retinas as well as in ARPE-19cells weredetected by ELISA assay. Furthermore, blood-retinal barrier permeabilityand ARPE-19cell viability were measured by Evans-Blue and cell countingkit-8assay, respectively.Results: HMGB1signaling pathway components including receptorsfor HMGB1as well as NF-кB and TNF-α/VEGF were significantly upregulated in type2diabetic retinas and in high glucose treated ARPE-19cells, compared to their respective counterparts. HMGB1blockagesignificantly alleviated NF-кB activity and VEGF secretion in ARPE-19cells cultured with high glucose. In addition, blood-retinal barrierpermeability of diabetic retinas increased, while cell viability of highglucose treated ARPE-19cells decreased.Conclusions: Expression of HMGB1signaling pathway componentswere increased in diabetic retinas and ARPE-19cells exposed to highglucose.
Keywords/Search Tags:diabetic retinopathy, HMGB1, inflammation, type2diabetes, ARPE-19
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