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Journal of Diabetes Research
Volume 2013 (2013), Article ID 589474, 10 pages
http://dx.doi.org/10.1155/2013/589474
Research Article

Impact of High Glucose and Proteasome Inhibitor MG132 on Histone H2A and H2B Ubiquitination in Rat Glomerular Mesangial Cells

Department of Endocrinology, Affiliated Hospital of Luzhou Medical College, Luzhou 646000, China

Received 28 October 2012; Revised 12 January 2013; Accepted 17 February 2013

Academic Editor: Aimin Xu

Copyright © 2013 Chenlin Gao et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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- (TGF- ), 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 , whereas it decreased significantly in intervention group . In contrast, H2B ubiquitination decreased with an increasing concentration of glucose, but it was recovered in the intervention group . Expression of TGF- 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- signaling pathway.