Clinical Scorecard: Sex-Dependent Effects of Epithelial Muscarinic Receptor 3 Knockout on Colonic Progenitor Cell Dynamics and Intestinal Injury Response
At a Glance
Category
Detail
Condition
Colonic epithelial homeostasis and injury response influenced by muscarinic receptor 3 signaling
Key Mechanisms
Epithelial M3 muscarinic acetylcholine receptor modulates colonic Lgr5+ progenitor cells and epithelial differentiation with sex-specific effects
Target Population
Male and female murine colonic epithelial cells; murine and human colonoids
Care Setting
Research and potential therapeutic targeting in colonic inflammatory diseases
Key Highlights
Genetic epithelial M3R ablation reduces Lgr5+ progenitor cells in male colons but expands them in females.
Male M3R knockout mice develop severe inflammation after acute colitis induction, females are largely protected.
Sex-specific effects of cholinergic and muscarinic signaling on epithelial cells confirmed in murine and human colonoids.
Guideline-Based Recommendations
Diagnosis
Consider sex-specific differences when evaluating colonic epithelial progenitor cell dynamics in research settings.
Management
Targeting cholinergic muscarinic receptor signaling may offer therapeutic potential in colonic inflammatory diseases.
Therapeutic strategies should account for sex-dependent responses to muscarinic receptor modulation.
Monitoring & Follow-up
Monitor inflammatory responses and epithelial progenitor cell populations with attention to sex differences during experimental colitis or therapeutic interventions.
Risks
Epithelial M3R ablation may exacerbate colitis severity in males, indicating potential sex-specific adverse effects.
Patient & Prescribing Data
Preclinical murine models and human colonoids representing male and female colonic epithelium
Cholinergic and muscarinic receptor agonism modulates epithelial homeostasis differently by sex, suggesting personalized approaches in therapy development.
Clinical Best Practices
Incorporate sex as a biological variable in studies of intestinal epithelial homeostasis and regeneration.
Consider regional differences in intestinal segments when evaluating muscarinic receptor functions.
Use murine and human colonoid models to validate sex-specific effects of cholinergic signaling on epithelial cells.
by Mohab Ragab, Jessica Wieland, Caroline Waldherr Avila de Melo, Tatiana Agibalova, Anastasia Ermolova, Niklas Durner, Anneke Hempel, Fabian Heindl, H Carlo Maurer, Katja Steiger, Klaus-Peter Janssen, Markus Tschurtschenthaler, Timothy C Wang, Michael Quante, Roland M Schmid, Moritz Middelhoff
