کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
10750184 1050297 2015 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
9-cis-retinoic acid improves sensitivity to platelet-derived growth factor-BB via RXRα and SHP-1 in diabetic retinopathy
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
9-cis-retinoic acid improves sensitivity to platelet-derived growth factor-BB via RXRα and SHP-1 in diabetic retinopathy
چکیده انگلیسی
Diabetic retinopathy (DR) is one of the most common complications of diabetes mellitus. But few efficient therapeutic methods have been reported. This study discussed the functions of 9-cis-retinoic acid (9-cis-RA) in sensitizing retinal pericytes to platelet-derived growth factor (PDGF)-BB. Using streptozotocin (STZ)-induced diabetic mice and high glucose-treated bovine retinal pericytes (BRPC), we analyzed the impacts of 9-cis-RA by detecting cell apoptosis via DNA fragmentation assay and detecting related factors through adenovirus or lentivirus infection and western blot. Results showed that in retinas of STZ-induced diabetic mice, 9-cis-RA significantly inhibited expression of SHP-1 (P < 0.01), thus promoting p-AKT and p-ERK1/2, which reflected the improved sensitivity to PDGF-BB. In BRPC, 9-cis-RA also improved sensitivity to PDGF-BB and suppressed cell apoptosis (P < 0.01) via down-regulating SHP-1. Further mechanism analyses showed that the efficient functioning of 9-cis-RA relied on the existence of its receptor, retinoic X receptor α (RXRα), independent of the previous reported protein kinase C delta (PKCδ)/SHP-1 axis. Because 9-cis-RA could not inhibit SHP-1 or improve sensitivity to PDGF-BB when RXRα was knocked down, while it still suppressed SHP-1 after overexpression of PKCδ. Taken together, these results indicated the vital roles of 9-cis-RA in improving sensitivity to PDGF-BB of retinal pericytes in DR, and provided basic evidences of new therapeutic targets like RXRα for further DR treatment.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical and Biophysical Research Communications - Volume 465, Issue 4, 2 October 2015, Pages 810-816
نویسندگان
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