Smoothelin expression in the gastrointestinal tract: implication in colonic inertia.
Colonic inertia is a frustrating motility disorder to patients, clinicians, and pathologists. The pathogenesis is largely unknown. The aims of this study were to: (1) characterize the expression of smoothelin, a novel smooth muscle-specific contractile protein expressed only by terminally differentiated smooth muscle cells, in the normal gastrointestinal (GI) tract; and (2) determine whether smoothelin is aberrantly expressed in patients with colonic inertia. A total of 57 resections of the normal GI tract (distal esophagus to left colon) were obtained from patients without GI motor dysfunction. Sixty-one colon resections were obtained from patients with a clinical diagnosis of colonic inertia. Smoothelin immunostaining was conducted on full-thickness tissue sections. In the nondysmotile controls, strong and diffuse cytoplasmic staining for smoothelin was observed in both the inner circular and outer longitudinal layers of the muscularis propria (MP) throughout the entire GI tract. The muscularis mucosae (MM) and muscular vessel walls were either completely negative or only patchily and weakly stained. The 1 exception to this pattern was observed in the distal esophagus, in which the MM was also diffusely and strongly stained. In cases with colonic inertia, a moderate to marked reduction of smoothelin immunoreactivity was observed in 15 of 61 (24.6%) colon resections, selectively seen in the outer layer of the MP. The data demonstrate that smoothelin is differentially expressed in the MP and MM of the normal GI tract and suggest that defective smoothelin expression may play a role in the pathogenesis of colonic inertia in a subset of patients.
*Department of Pathology and Laboratory Medicine ∥Gastrointestinal Motility Program, Division of Gastroenterology, Cedars-Sinai Medical Center ¶Department of Pathology & Laboratory Medicine, University of California, Los Angeles, Los Angeles, CA †Department of Anatomical Pathology, Cleveland Clinic Foundation, Cleveland, OH ‡Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY §Department of Pathology, University of Chicago Hospitals, Chicago, IL.
Owen T M
OT
Chan
Lauren
L
Chiles
Mary
M
Levy
Jing
J
Zhai
Lisa M
LM
Yerian
Haodong
H
Xu
Shu-Yuan
SY
Xiao
Edy E
EE
Soffer
Jeffrey L
JL
Conklin
Deepti
D
Dhall
Melissa E
ME
Kahn
Bonnie L
BL
Balzer
Mahul B
MB
Amin
Hanlin L
HL
Wang
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002675:Child, Preschool; D003248:Constipation / Q000175:diagnosis* / Q000473:pathology; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D015154:Esophageal Motility Disorders / Q000175:diagnosis* / Q000473:pathology; D005260:Female; D041981:Gastrointestinal Tract / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009092:Mucous Membrane / Q000378:metabolism* / Q000473:pathology; D009119:Muscle Contraction; D009124:Muscle Proteins / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000378:metabolism / Q000473:pathology; D012189:Retrospective Studies; D055815:Young Adult
D003598:Cytoskeletal Proteins; D009124:Muscle Proteins; C100762:SMTN protein, human