Analyses of PRMT1 proteins in human colon tissues from Hirschsprung disease patients.

ABSTRACT

BACKGROUND: Protein arginine methyltransferase 1 (PRMT1) catalyzes the majority of arginine methylation in cells and plays important roles in the differentiation and development of neurons. It is also implicated in the regulation of nitric oxide synthetase (NOS). Hirschsprung disease (HSCR) is characterized by the absence of intramural ganglion cells in the nerve plexuses of the distal gut. METHODS: Western blot analyses revealed reduced PRMT1 protein levels in the aganglionosis segments of HSCR patients. Immunohistochemistry detected PRMT1 expression in the colonic mucosa, the enteric nervous system (ENS) and endothelial cells. Specific and strong PRMT1 expression in neuron cell bodies of the plexus was demonstrated by immunofluorescent double-labeling with neuron-specific marker HuC/D. KEY RESULTS: In the mucosa, PRMT1 was detected at all crypt cells. Intensive PRMT1 staining was detected in the submucosal and the myenteric plexuses in normal or oligoganglionosis segments. Aganglionosis segments from HSCR patients contain no plexuses, and thus not labeled with PRMT1. The phenomenon is specific to the megacolon of HSCR as strong PRMT1 staining was observed in plexuses of the rectal ectasia segments (dilated rectum and distal sigmoid not related with aganglionosis) from anorectal malformation patients. Furthermore, PRMT1 was also present in the same neuronal cells expressing neuronal NOS in the plexuses. CONCLUSIONS & INFERENCES We suggest that PRMT1 can be a useful marker for HSCR. This study is the first illustration of PRMT1 protein expression in human tissues from non-cancerous disease and set up the base for further investigations of PRMT1 function in ENS development and intestinal motility.