Characterization of Expression of a Novel Smooth Muscle Contractile Protein Smoothelin in Gastrointestinal Tract: Implication in the Pathogenesis of Colonic Inertia
L Chiles, M Levy, BL Balzer, H Xu, SY Xiao, J Zhai, E Soffer, J Conklin, D Dhall, ME Kahn, MB Amin, HL Wang. Cedars-Sinai Medical Center, Los Angeles; University of Rochester Medical Center, Rochester; University of Texas, Galveston
Background: Colonic inertia (CI) is a frustrating motility disorder not only to clinicians but also to pathologists. Its etiopathogenesis is largely unknown. The aim of this study was to characterize the expression of smoothelin, a novel contractile protein expressed only by fully differentiated smooth muscle cells, in normal gastrointestinal (GI) tract and to determine if smoothelin is aberrantly expressed in patients with CI.
Design: A total of 67 resections of normal GI tract from patients with dysmotility-unrelated disorders (distal esophagus 3, stomach 4, duodenum 12, ampulla 10, jejunum 7, ileum 11, right colon 10 and left colon 10) and 28 colon resections (16 with terminal ileum) from patients with CI were included in this study. Full-thickness and well-oriented sections were selected for immunostaining for smoothelin. Staining for smooth muscle actin (SMA) was used for comparison.
Results: In controls, strong and diffuse cytoplasmic staining for smoothelin was observed in both inner and outer layers of the muscularis propria (MP) throughout the entire GI tract. In contrast, the muscularis mucosae (MM) were either completely negative or only patchy and weakly stained with the exception of the distal esophagus where the MM was also strongly and diffusely stained. In CI patients, a moderate to marked reduction in smoothelin immunoreactivity was observed in 16 of 28 (57.1%) colon resections exclusively in the outer layer of the MP, compared to normally stained inner layer. Of these 16 cases, a similar reduction in smoothelin immunoreactivity was also observed in 3 (18.8%) ileal resections. SMA stained both inner and outer layers strongly and diffusely in all colon resections. In contrast, a moderate to marked reduction in SMA immunoreactivity, exclusively in the inner layer of the MP, was observed in 9 (56.3%) ileal resections, of which 4 had reduced smoothelin expression in the colon and 2 in both colon and ileum.
Conclusions: Smoothelin is differentially expressed in the MP and MM of the GI tract, which may be of potential utility in cases where the distinction between the two is necessary. Defective smoothelin expression in the presence of essentially normal histologic findings and the preservation of SMA immunoreactivity suggests a role in the pathogenesis of CI.
Wednesday, March 11, 2009 9:30 AM
Poster Session V # 87, Wednesday Morning