Increased population of immature enteric glial cells in the resected proximal ganglionic bowel of Hirschsprung's disease patients

Abstract

Background: Enteric glial cells are essential for normal gastrointestinal function. Abnormalities in glial structure, development, or function lead to disturbances in gastrointestinal physiology. Fatty acid-binding protein 7 (FABP7) is a marker of immature enteric glial cells, whereas S100 is expressed only by mature glial cells. Patients with Hirschsprung's disease (HSCR) often suffer from dysmotility and enterocolitis despite proper surgery. We designed this study to determine the distribution and expression of glial cells in patients with HSCR compared to normal controls.

Methods: We investigated FABP7, S100, and PGP 9.5 expressions in both the ganglionic and aganglionic bowel of patients with HSCR (n = 6) versus normal control colon (n = 6). Protein distribution was assessed by using immunofluorescence and confocal microscopy. Gene and protein expressions were quantified using quantitative real-time polymerase chain reaction (qPCR), Western blot analysis, and densitometry.

Results: qPCR and Western blot analysis demonstrated a significantly increased FABP7 expression in ganglionic specimens compared to control specimen (P < 0.05). Confocal microscopy revealed FABP7⁺ glia cells lie under the colonic epithelium and in close apposition to enteric neurons in the ganglionic bowel.

Conclusions: The significantly increased number of immature enteric glial cells (EGCs) in the ganglionic bowel of HSCR patients may have adverse effect on the function of enteric neurons and intestinal barrier and thus predispose these patients to intestinal motility problems and enterocolitis.

Keywords: Enteric glial cells; Fatty acid–binding protein 7; Hirschsprung's disease; Premature glia.