TRPV4-Dependent Epithelial Mechanoadaptation and Barrier Remodeling Mediate Sennoside-Induced Distal Colonic Motility

Improvement of bowel function is accompanied by increased luminal flow and altered epithelial mechanical forces, yet the underlying epithelial mechanisms remain unclear. We investigated whether enhanced luminal stimulation is associated with epithelial mechanotransduction and junctional remodeling during changes in colonic motility. Sennoside was orally administered at 4.8 mg/kg body weight to 5-week-old male BALB/cAJcl mice for 21 days to model increased luminal stimulation. Stool characteristics, fecal water content, Bristol Stool Form Scale scores, and segmental colonic motility were assessed. Expression of Muc2, inflammatory cytokines, Trpv4, and E-cadherin was quantified across colonic regions. In CT26 monolayers, mechanical stress was applied to evaluate transient receptor potential channel induction, E-cadherin redistribution, and transepithelial electrical resistance, and the effect of Trpv4 knockdown. Sennoside softened stools, increased fecal water content (+18%) and Bristol scores (+57%), and enhanced distal colonic motility (+117%) without altering inflammatory cytokines. Trpv4 was selectively upregulated in the distal colon (3.3-fold). E-cadherin expression increased (2.5-fold) with junctional redistribution, whereas Muc2 decreased (-44%). In vitro, mechanical stress upregulated Trpv4 (2.5-fold), increased barrier resistance (+48%), and promoted E-cadherin assembly; these effects were augmented by sennoside and attenuated by Trpv4 silencing. These findings suggest that epithelial responses involving TRPV4-associated mechanotransduction and junctional remodeling are associated with altered barrier-related properties and distal colonic functional changes, providing insight into an epithelial component of stimulant laxative action.