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@ARTICLE{Ragab:299568,
author = {M. Ragab and J. Wieland and C. W. Ávila de Melo and T.
Agibalova and A. Ermolova and N. Durner and A. Hempel and F.
Heindl and H. C. Maurer and K. Steiger and K.-P. Janssen and
M. Tschurtschenthaler$^*$ and T. C. Wang and M. Quante and
R. M. Schmid and M. Middelhoff},
title = {{E}pithelial {G}enetic {M}uscarinic {R}eceptor 3 {A}blation
{I}nduces {S}ex-{S}pecific {M}odulation of {C}olonic
{I}ntestinal {P}rogenitor {C}ells and {R}esponse to
{I}ntestinal {I}njury.},
journal = {Journal of Crohn's and Colitis},
volume = {19},
number = {6},
issn = {1873-9946},
address = {Oxford},
publisher = {Oxford Univ. Press},
reportid = {DKFZ-2025-00509},
pages = {jjaf038},
year = {2025},
note = {2025 Jun 4;19(6):jjaf038},
abstract = {Epithelial muscarinic acetylcholine receptor subtype 3
(M3R) signaling modulates intestinal stem and progenitor
cell function, yet its impact on colonic homeostasis remains
unclear. Hence, this study explores sex-specific effects of
epithelial genetic M3R ablation and muscarinic receptor
agonism on murine colonic Lgr5-EGFP+ progenitor cells and
epithelial homeostasis.Genetic ablation of M3R was achieved
using Vil-Cre x M3R fl/fl mice. The effects on
Lgr5-expressing progenitor cells, epithelial homeostasis and
response to intestinal injury were assessed, with attention
to sex-specific differences. Effects of cholinergic,
muscarinic agonism on epithelial cell homeostasis were
evaluated employing murine and human colonoids.Genetic
epithelial ablation of the M3R employing Vil-Cre x M3R fl/fl
mice interestingly resulted in the prominent reduction in
Lgr5-expressing progenitor cells in male tissues,
contrasting an expansion of Lgr5-expressing cells in female
colonic epithelia. This difference showed abrogated in young
female Vil-Cre x M3R fl/fl mice, which harbor reduced
circulating sex hormone levels. Genetic M3R ablation further
induced changes to epithelial differentiation. Importantly,
male Vil-Cre x M3R fl/fl mice developed severe inflammation
following induction of acute experimental colitis, which did
almost not affect female Vil-Cre x M3R fl/fl mice. Moreover,
sex-specific effects of modulations of cholinergic,
muscarinic signaling on epithelial cells could be
corroborated in murine and human colonoids.Our data reveal
sex differences in the modulation of intestinal, colonic
epithelial cells by cholinergic, muscarinic signaling and
highlight the potential for therapeutic strategies targeting
cholinergic receptor signaling in colonic inflammatory
diseases.},
keywords = {Colonic progenitor cells (Other) / Epithelial muscarinic
receptor 3 (Other) / colitis (Other)},
cin = {MU01},
ddc = {610},
cid = {I:(DE-He78)MU01-20160331},
pnm = {899 - ohne Topic (POF4-899)},
pid = {G:(DE-HGF)POF4-899},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:40052554},
doi = {10.1093/ecco-jcc/jjaf038},
url = {https://inrepo02.dkfz.de/record/299568},
}