Epigenetics: new insights into postoperative adhesion development.

Abstract

The link between post-operative adhesion development and epigenetic modifications is important in understanding the mechanism behind their formation. The purpose of this study was to determine whether epigenetic differences exist between primary fibroblasts of normal peritoneum and adhesion tissues isolated from the same patient(s). DNA from fibroblasts isolated from normal peritoneum and adhesion tissues was isolated using Qiagen's EZ1 Advanced Kit. Methylation patterns of genes were quantified and compared in both cell lines using the Infinium Human Methylation 27 Beadchip system. A total of 7364 genes had been found to manifest significantly different DNA methylation levels in adhesion fibroblasts as compared to normal peritoneal fibroblasts (p<0.01). A total of 1685 genes were found to have increased DNA methylation by 50% in adhesion compared to peritoneal fibroblasts, and were enriched in Gene Ontology categories, Glycoprotein, and Defense Response. Furthermore, 1287 genes were found to have decreased DNA methylation patterns with enriched Gene Ontology categories, "Homeobox", and Transcription Factor Activity in adhesion fibroblasts. Epigenetic differences in fibroblasts isolated from normal peritoneum and adhesion tissues were observed. Future studies focusing on the precise role of these genes in the development of post operative adhesions will allow us to more fully appreciate regulatory mechanisms leading to adhesion development, thereby establishing targets for therapeutic interventions to prevent or limit adhesion development.