Colonic smooth muscle cells and interstitial cells of Cajal in diverticular disease

Intestinal motility is regulated by complex interactions among smooth muscle cells (SMC) of muscularis propria, enteric nerve endings and interstitial cells of Cajal (ICC). In colonic SMC, transmenbrane channels rich in connexin (Cx), in particular Cx43, contribute to intercellular gap junctions, which ensure coordinated motor responses to nerve inputs. ICC are pacemaker cells which modulate neuroenteric transmission by connecting SMC with varicosities of myenteric neuron axons. There is evidence that SMC motility and gap junction permeability are regulated by the GTPase RhoA, an emerging key modulator of SMC phenotype. The purpose of the present study was to evaluate the patterns of Cx43 and RhoA expression in SMC, as well as ICC density in colonic specimens from patients affected by diverticular disease (DD), a condition associated with colonic motor dysfunction. The muscularis propria of surgical whole thickness colonic samples from DD patients was examined immunohistochemically for the expression of Cx43 and RhoA in SMC, and c-kit in ICC. Semiquantitative analysis of DD colonic specimens displayed a marked decrease in Cx43 and RhoA expression in SMC. There was also a reduced ICC density in myenteric ganglia (ICC-MY), circular (ICC-CM) and longitudinal (ICC-LM) muscle, as compared to controls. Overall, it is suggested that abnormalities in gap junctions and RhoA expression in SMC, together with a reduced density of muscular ICC, account for the colonic dismotility occurring in DD.