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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},
}