Yankai Xia
Nanjing Medical University, China
Title: Multiple 'omics'-Analysis Reveals the Role of Prostaglandin E2 in Hirschsprung’s Disease
Biography
Biography: Yankai Xia
Abstract
The etiology and pathogenesis of Hirschsprung’s disease (HSCR) remain largely unknown. Here we employed a multiple ‘omics’-analysis to explore the important pathway related to the development of HSCR. We examined colon tissues from three independent populations with a combined analysis of metabolomics, transcriptomics and proteomics to understand HSCR. Mouse model was used for examining PGE2 induced clinical presentation of HSCR. SH-SY5Y and SK-N-BE(2) cell lines were used for examining PGE2 inhibited cell migration through EP2.The integrated analysis suggests that the level of PGE2, the expression of the genes encoding its receptor (EP2) (PTGER2) and PGE2 synthesis enzyme genes (PTGS1 and PTGES) increased in HSCR colon tissues, together with a decreased synthesis of PGE2-related byproducts. In animal study, the pregnant mice treated with PGE2 gave birth to offspring with the lack of gangliocytes in colon and gut mobility. In vitro study, we confirmed that, when EP2 was blocked, the PGE2-inhibited migration of neural cell was recovered. Our study identified a novel pathway linking expression of PTGS1 and PTGES, level of PGE2, expression of PTGER2, and neural cell migration in HSCR, providing a novel avenue for the future diagnosis and prevention of HSCR.