【摘 要】
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Aims/hypothesis: Inflammation plays important roles in the development of diabetic retinopathy (DR).How the müller cell contributes to DR-related inflammation remains unclear.We hypothesized that unde
【机 构】
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College of Life Sciences Wuhan University China
【出 处】
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BIT`s 3rd Annual World Congress of NeuroTalk-2012(2012第三届国际神
论文部分内容阅读
Aims/hypothesis: Inflammation plays important roles in the development of diabetic retinopathy (DR).How the müller cell contributes to DR-related inflammation remains unclear.We hypothesized that under diabetic condition, elevated histone acetylations in the müller cell contributes to the inflammatory response.Minocycline, a drug known to have beneficial effects on DR, may function through manipulating hyperglycemia induced histone acetylation.Methods: Specific histone acetylation sites, levels of histone acetyltranferases and deacetylases, and müller cell activation were investigated by western blots in the retinas of diabetic rodents and the high glucose (HG) cultured müller cells.Co-staining of AcH3K9 and AcH3K18 with S 100 were performed on retinal sections.Inflammatory transcription factors, inflammatory genes, and the binding affinities of acetylated H3K9 and H3K18 on the promoters of inflammatory genes were investigated in the HG cultured müller cells with or without minocycline.Results: Significantly increased in histone acetylation, histone acetyltranferases levels with decreased in histone deacetylases levels were found in the retinas of diabetic rats.Elevated AcH3K9 and AcH3K18 were partially costained with müller cells in the retinal sections.HG induced upregulation of acetylated histones, GFAP, p-STAT3 and NFκβ-p65, and inflammatory genes, TNFα and MCP-1 in cultured müller cells.Minocycline reduced HG induced müller cell activation, inflammation and acetylated H3K 18 bound to the promoters of inflammatory genes.Conclusions/interpretation: These data indicated the histone acetylation in müller cells plays an important role in the procession of DR.Inhibition of histone acetylation by minocycline is a novel function that contributes to its beneficial effects on DR.
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