Novel smooth muscle markers reveal abnormalities of the intestinal musculature in severe colorectal motility disorders.
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 alpha-actin (alpha-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-alpha-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 alpha-SMA, suggesting specific defects of smooth muscle cells involved in the pathogenesis of gastrointestinal motility disorders.
Wedel
T
T
Department of Anatomy, University of Luebeck, Luebeck, Germany. t.wedel@anat.uni-kiel.de
Van Eys
G J J M
GJ
Waltregny
D
D
Glénisson
W
W
Castronovo
V
V
Vanderwinden
J-M
JM
D000199:Actins / Q000378:metabolism; D015415:Biomarkers; D003108:Colonic Diseases / Q000378:metabolism* / Q000473:pathology*; D003598:Cytoskeletal Proteins / Q000378:metabolism; D005769:Gastrointestinal Motility / Q000502:physiology*; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D046529:Microscopy, Electron, Transmission; D009124:Muscle Proteins / Q000378:metabolism; D009130:Muscle, Smooth / Q000378:metabolism* / Q000473:pathology*; D018995:Myosin Heavy Chains / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism
D000199:Actins; D015415:Biomarkers; D003598:Cytoskeletal Proteins; D009124:Muscle Proteins; D012097:Repressor Proteins; C100762:SMTN protein, human; C409470:HDAC8 protein, human; D006655:Histone Deacetylases; D018995:Myosin Heavy Chains