Novel epigenetic-sensitive clinical challenges both in type 1 and type 2 diabetes

表观遗传学 医学 DNA甲基化 2型糖尿病 内分泌学 内科学 癌症研究 糖尿病 生物 基因表达 遗传学 基因
作者
Linda Sommese,Giuditta Benincasa,Michele Lanza,Antonio Sorriento,Concetta Schiano,Roberta Lucchese,Roberto Alfano,Giovanni Francesco Nicoletti,Claudio Napoli
出处
期刊:Journal of Diabetes and Its Complications [Elsevier BV]
卷期号:32 (11): 1076-1084 被引量:45
标识
DOI:10.1016/j.jdiacomp.2018.08.012
摘要

Epigenetics modulated tissue-specific gene expression during the onset of type 1 and type 2 diabetes and their complications.We searched the PubMed recent studies about the main epigenetic tags involved in type 1 and type 2 diabetes onset and their clinical complications. PubMed studies about the epigenetic tags involved in type 1 and 2 diabetes onset was searched.The epigenetic methylation maps of cord blood samples highlighted differences in the methylation status of CpG sites within the MHC genes between carriers of diabetes type 1 DR3-DQ2 and DR4-DQ8 risk haplotypes. β cell-derived unmethylated INS DNA showed the decline of β-cell mass preserving insulin secretion. Differentially methylated regions in pancreatic islets from type 2 diabetes covered PDX1, TCF7L2, and ADCY5 promoters during islet dysfunction. The recruitment of SET7 and SUV39H1 histone methyltransferases and LSD-1 lysine-specific demethylase-1 at NF-kβ-p65 promoter in vascular cells was involved in coronary heart disease. Neutrophil extracellular trap, activated by protein arginine deiminase-4, impaired wound healing from diabetic foot ulcers. MiR-199a-3p over-expression induced coagulative cascade, swelling and pain by a down-regulation of SERPIN-E2 in diabetic peripheral neuropathy. A DNA hypo-methylation and histone hyper-acetylation at MIOX promoter led an overexpression of ROS, fibronectin, HIF-1α, and NOX-4 associated with diabetic tubulopathy. A hypo-methylation of H3K4 at SOD2 promoter by LSD-1 increased ROS causing diabetic retinopathy.Epigenetics played a relevant role in prevention, diagnosis, and treatment of diabetes.
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