Diabetic patients suffer from slow wound healing even after their sugar level is brought to normal levels. Even the cells isolated from the body of the diabetic patients show inflammatory behaviour in vitro(inside test tube). This metabolic memory of diabetic cells is attributed to the histones-the proteins that bind to DNA. Ultimately the modification of histones alter their binding to the DNA, the DNA expression and protein translation.
A number of experiments conducted in vitro have revealed that the methylation of histones( particularly the lysine of histone 3) occurs at a very low rate in case of diabetic cells. SET family of proteins are crucial to methylate the lysine in particular. Upregulation of the family Svu39, that belongs to SET, increased the methylation in histones. This study was performed using chromatin immunoprecipitation assays( Chip assays) and real time PCR(polymerase chain reaction). The inflammatory behaviour was then studied for these cells. The decreased inflammatory response observed in these cells meant a faster healing of cells.
To make sure that Svu family stimulated faster healing , in normal cells this family of proteins was artificially inhibited and the result was higher inflammation.
Normal cells from mice were then tested in media with different glucose concentrations, for the level of lysine methylation . In coherence with the previous experiments the methylation was really low in case of cells cultured in a high glucose media(25mM).
Hence the wounds in diabetic patients can be healed better if histones are methylated at the epigenetic level. This would mean a drug to target Svu family and upregulate it would promote methylation and faster wound healing. Work in this field is being done by Louisa M. Villeneuve, Marpadga A. Reddy, Linda L. Lanting etal,Department of Diabetes, Beckman Research Institute of City of Hope, Duarte.