Abstract
Background. Hyperglycemia plays a pivotal role in the development of diabetic nephropathy (DN) and may be related to epigenetic metabolic memory. One of the most crucial epigenetic mechanisms is histone modification, which is associated with the expression of a fibrosis factor in vascular injury. Aim .In this study, we investigated the ubiquitination of histones H2A and H2B to explore the epigenetic mechanisms of DN. Materials and Methods. The GMCs were cultured as follows: normal group, high glucose group, mannitol group, and intervention group. After 12 hr, 24 hr, and 48 hr, histones ubiquitination, transforming growth factor-β (TGF-β), and fibronectin (FN) were measured using WB, RT-PCR, and IF. Result. High glucose can induce the upregulation of FN. H2A ubiquitination in GMCs increased in high glucose group (P < 0.01), whereas it decreased significantly in intervention group (P < 0.05). In contrast, H2B ubiquitination decreased with an increasing concentration of glucose, but it was recovered in the intervention group (P < 0.05). Expression of TGF-β changed in response to abnormal histone ubiquitination. Conclusions. The high glucose may induce H2A ubiquitination and reduce H2B ubiquitination in GMCs. The changes of histone ubiquitination may be due in part to DN by activating TGF-β signaling pathway.
Highlights
Diabetic nephropathy (DN) is one of the most devastating microvascular complications of diabetes, which remains the most common cause for end stage renal disease (ESRD)
We evaluated the influence of high glucose on the induction of histone H2A ubiquitination, reduced histone H2B ubiquitination in GCMs, and changes in the expression of transforming growth factor-β (TGF-β) followed by abnormal histone ubiquitination
There were no significant differences in H2B ubiquitination expression in the 10 mmol/L high glucose group compared to the NC group (P = 0.327)
Summary
Diabetic nephropathy (DN) is one of the most devastating microvascular complications of diabetes, which remains the most common cause for end stage renal disease (ESRD). Diabetic complications, including chronic kidney disorders such as DN, have been shown to persist and progress even after glucose control has been achieved, possibly as a result of prior episodes of hyperglycemia that are considered the epigenetic metabolic memory [7]. Preliminary work using endothelial cells has shown that transient episodes of hyperglycemia can induce changes in gene expression that are dependent on the modification of histone tails (i.e., methylation) [8]. The persistence of such modifications has not been fully explained. The changes of histone ubiquitination may be due in part to DN by activating TGF-β signaling pathway
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