Loss of interstitial cells of Cajal and development of electrical dysfunction in murine small bowel obstruction

Abstract

1. Partial obstruction of the murine ileum led to changes in the gross morphology and ultrastructure of the tunica muscularis. Populations of interstitial cells of Cajal (ICC) decreased oral, but not aboral, to the site of obstruction. Since ICC generate and propagate electrical slow waves in gastrointestinal muscles, we investigated whether the loss of ICC leads to loss of function in partial bowel obstruction.2. Changes in ICC networks and electrical activity were monitored in the obstructed murine intestine using immunohistochemistry, electron microscopy and intracellular electrophysiological techniques.3. Two weeks following the onset of a partial obstruction, the bowel increased in diameter and hypertrophy of the tunica muscularis was observed oral to the obstruction site. ICC networks were disrupted oral to the obstruction, and this disruption was accompanied by the loss of electrical slow waves and responses to enteric nerve stimulation. These defects were not observed aboral to the obstruction. 6. These data describe the plasticity of ICC networks in response to partial obstruction. After obstruction the ICC phenotype was lost, but these cells regenerated when the obstruction was removed. This model may be an important tool for evaluating the cellular/molecular factors responsible for the regulation and maintenance of the ICC phenotype.

Are interstitial cells of Cajal plurifunction cells in the gut?

“…The creation of experimental partial obstruction in the small intestine alters the structure and phenotype of the ICC oral to the site of obstruction so that they become more like myofibroblasts (26). This transformation occurs with decreasing intensity up to about 10 cm oral to the site of partial obstruction.…”

“…This transformation of the ICC to fibroblasts or smooth muscle-like cells may occur as soon as within 5 h after intestinal resection (196). Reverse transformation of the ICC occurs as soon as the microenvironment returns to the normal state (26,196).…”

Molecular and Cellular Characteristics of the Colonic Pseudo-obstruction in Patients With Intractable Constipation

“…6 and 7). Extensive luminal dilation with smooth muscle hypertrophy developed proximally to the TZ region closely resembles the results of partial occlusion mechanically induced in laboratory animals, 29,30 which lead us to speculate that the TZ is the site of high resistance due to functional obstruction. Accumulation of the fecal contents proximally may result in passive stretch and luminal dilation, leading to smooth muscle hypertrophy as an adaptation to increased functional demand.…”

Serum Response Factor Is Essential for Prenatal Gastrointestinal Smooth Muscle Development and Maintenance of Differentiated Phenotype

“…To test our hypothesis, we looked for changes in SRF expression in hypertrophic GI tissue using a surgically induced partial obstruction mouse model. 10 Two weeks after placement of a small silicon ring on the distal ileum, the jejunum and ileum were severely distended compared to the large ring sham control ( Fig. 2A).…”

“…10 Briefly, a silicon ring was surgically placed on the distal ileum just oral to the cecum. As a modification to the previously described protocol, a 5-0 polyglycolic acid suture was placed through the ends of the silicon ring opening to secure its closing.…”