Hirschsprung disease(HSCR)is a congenital anomaly of the intestine caused by the developmental absence of the enteric nervous system,which results in variable lengths of intestinal dysfunction and requires surgical intervention.^([1])Due to the complex etiology,multiple surgical procedures and postoperative complications,the diagnosis and treatment strategies of HSCR have always been the focus of pediatric surgeons around the world.Seventy pediatric surgical experts with rich clinical experience from almost all national and provincial children’s medical centers in China constituted the Chinese Research Group of Hirschsprung disease(CRGHSCR).
Tianqi ZhuWeibing TangJiexiong Fengthe Chinese Research Group of Hirschsprung Disease
Endogenous peptides,bioactive agents with a small molecular weight and outstanding absorbability,regulate various cellular processes and diseases.However,their role in the occurrence of Hirschsprung’s disease(HSCR)remains unclear.Here,we found that the expression of an endogenous peptide derived from YBX1(termed PDYBX1 in this study)was upregulated in the aganglionic colonic tissue of HSCR patients,whereas its precursor protein YBX1 was downregulated.As shown by Transwell and cytoskeleton staining assays,silencing YBX1 inhibited the migration of enteric neural cells,and this effect was partially reversed after treatment with PDYBX1.Moreover,immunoprecipitation and immunofluorescence revealed that ERK2 bound to YBX1 and PDYBX1.Downregulation of YBX1 blocked the ERK1/2 pathway,but upregulation of PDYBX1 counteracted this effect by binding to ERK2,thereby promoting cell migration and proliferation.Taken together,the endogenous peptide PDYBX1 may partially alleviate the inhibition of the ERK1/2 pathway caused by the downregulation of its precursor protein YBX1 to antagonize the impairment of enteric neural cells.PDYBX1 may be exploited to design a novel potential therapeutic agent for HSCR.
