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Critical role of the cAMP-PKA pathway in hyperglycemia-induced epigenetic activation of fibrogenic program in the kidney.

FASEB J.. 2017-02; 
Deb DK, Bao R, Li YC.
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摘要

Hyperglycemia is a major pathogenic factor that promotes diabetic nephropathy, but the underlying mechanism remains incompletely understood. Here, we show that high glucose induced cAMP response element-binding protein (CREB)-binding protein (CBP)-mediated H3K9/14 hyperacetylation in approximately 5000 gene promoters in glomerular mesangial cells, including those of Tgfb1, Tgfb3, and Ctgf, the major profibrotic factors that are known to drive diabetic renal fibrogenesis. In these promoters, H3K9/14 hyperacetylation was closely associated with NF-κB or CREB motifs. Chromatin immunoprecipitation assays confirmed that hyperglycemia promoted phospho-p65 or phospho-CREB and CBP bindings and RNA polymerase II r... More

关键词

ChIP-Seq; diabetic complication; histone acetylation; protein kinase A; renal fibrosis