Epithelial genetic muscarinic receptor 3 ablation induces sex-specific modulation of colonic intestinal progenitor cells and response to intestinal injury - Summary - MDSpire

Epithelial genetic muscarinic receptor 3 ablation induces sex-specific modulation of colonic intestinal progenitor cells and response to intestinal injury

  • 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

  • March 7, 2025

  • 0 min

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Objective:

To explore the sex-specific effects of genetic ablation of epithelial M3R and muscarinic receptor agonism on colonic progenitor cells and epithelial homeostasis.

Key Findings:
  • M3R ablation resulted in a reduction of Lgr5-expressing progenitor cells in males, while females showed an expansion.
  • Young female mice with reduced sex hormone levels did not exhibit the expansion of Lgr5-expressing cells.
  • Male M3R knockout mice developed severe inflammation after acute colitis induction, unlike females.
  • Sex-specific effects of cholinergic and muscarinic signaling were confirmed in both murine and human colonoids.
Interpretation:

The study reveals significant sex differences in how cholinergic, muscarinic signaling modulates intestinal epithelial cells, suggesting potential therapeutic strategies targeting this pathway in colonic inflammatory diseases.

Limitations:
  • The study primarily focuses on murine models, which may not fully translate to human physiology, potentially limiting the applicability of findings.
  • The long-term effects of M3R ablation on colonic health were not assessed, which may overlook chronic implications.
Conclusion:

Cholinergic receptor signaling plays a crucial role in colonic epithelial homeostasis and regeneration, with distinct sex-specific responses that could inform future therapeutic approaches, particularly in the context of existing research.

Original Source(s)

Epithelial genetic muscarinic receptor 3 ablation induces sex-specific modulation of colonic intestinal progenitor cells and response to intestinal injury

  • 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

  • March 7, 2025

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