Authors: wedel, t.¹; van eys, g. j. j. m.²; waltregny, d.³; glénisson, w.³; castronovo, v.³; vanderwinden, j-m.⁴

Source: Neurogastroenterology and Motility, Volume 18, Number 7, July 2006 , pp. 526-538(13)

Publisher: Wiley-Blackwell

Abstract:

 

Histopathological studies of gastrointestinal motility disorders have mainly focused on enteric nerves and interstitial cells of Cajal, but rarely considered the enteric musculature. Here we used both classical and novel smooth muscle markers and transmission electron microscopy (TEM) to investigate muscular alterations in severe colorectal motility disorders. Full-thickness specimens from Hirschsprung's disease, idiopathic megacolon, slow-transit constipation and controls were stained with haematoxylin/eosin (HE) and Masson's trichrome (MT), incubated with antibodies against smooth muscle α-actin (α-SMA), smooth muscle myosin heavy chain (SMMHC), smoothelin (SM) and histone deacetylase 8 (HDAC8) and processed for TEM. Control specimens exhibited homogeneous immunoreactivity for all antibodies. Diseased specimens showed normal smooth muscle morphology by HE and MT. While anti-α-SMA staining was generally normal, immunoreactivity for SMMHC, HDAC8 and/or SM was either absent or focally lacking in Hirschsprung's disease (80%), idiopathic megacolon (75%) and slow-transit constipation (70%). Ultrastructurally, clusters of myocytes with noticeably decreased myofilaments were observed in all diseases. SMMHC and the novel smooth muscle markers SM and HDAC8 often display striking abnormalities linked to the smooth muscle contractile apparatus unnoticed by both routine stainings and α-SMA, suggesting specific defects of smooth muscle cells involved in the pathogenesis of gastrointestinal motility disorders.

Keywords: colorectal motility disorders; histone deacetylase 8; smooth muscle α-actin; smooth muscle myosin heavy chain; smoothelin; ultrastructure

Document Type: Research article

DOI: http://dx.doi.org/10.1111/j.1365-2982.2006.00781.x

Affiliations: 1: Department of Anatomy, University of Luebeck, Luebeck, Germany 2: Department of Molecular Genetics, University of Maastricht, Maastricht, The Netherlands 3: Metastasis Research Laboratory, University of Liège, Liège, Belgium 4: Institute of Neurophysiology, Université Libre de Bruxelles, Brussels, Belgium

Publication date: 2006-07-01

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