Sympathetic activity regulates epithelial proliferation and wound healing via adrenergic receptor α 2A .

Autor: Ten Hove AS; Tytgat Institute for Liver and Intestinal Research, Gastroenterology and Hepatology, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam UMC, University of Amsterdam, Meibergdreef 69-71, 1105 BK, Amsterdam, The Netherlands. a.s.tenhove@amsterdamumc.nl., Mallesh S; Department of General, Visceral-, Thoracic and Vascular Surgery, University Hospital Bonn, Bonn, Germany., Zafeiropoulou K; Tytgat Institute for Liver and Intestinal Research, Gastroenterology and Hepatology, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam UMC, University of Amsterdam, Meibergdreef 69-71, 1105 BK, Amsterdam, The Netherlands., de Kleer JWM; Tytgat Institute for Liver and Intestinal Research, Gastroenterology and Hepatology, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam UMC, University of Amsterdam, Meibergdreef 69-71, 1105 BK, Amsterdam, The Netherlands., van Hamersveld PHP; Tytgat Institute for Liver and Intestinal Research, Gastroenterology and Hepatology, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam UMC, University of Amsterdam, Meibergdreef 69-71, 1105 BK, Amsterdam, The Netherlands., Welting O; Tytgat Institute for Liver and Intestinal Research, Gastroenterology and Hepatology, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam UMC, University of Amsterdam, Meibergdreef 69-71, 1105 BK, Amsterdam, The Netherlands., Hakvoort TBM; Tytgat Institute for Liver and Intestinal Research, Gastroenterology and Hepatology, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam UMC, University of Amsterdam, Meibergdreef 69-71, 1105 BK, Amsterdam, The Netherlands., Wehner S; Department of General, Visceral-, Thoracic and Vascular Surgery, University Hospital Bonn, Bonn, Germany., Seppen J; Tytgat Institute for Liver and Intestinal Research, Gastroenterology and Hepatology, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam UMC, University of Amsterdam, Meibergdreef 69-71, 1105 BK, Amsterdam, The Netherlands., de Jonge WJ; Tytgat Institute for Liver and Intestinal Research, Gastroenterology and Hepatology, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam UMC, University of Amsterdam, Meibergdreef 69-71, 1105 BK, Amsterdam, The Netherlands. w.j.dejonge@amsterdamumc.nl.; Department of General, Visceral-, Thoracic and Vascular Surgery, University Hospital Bonn, Bonn, Germany. w.j.dejonge@amsterdamumc.nl.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2023 Oct 20; Vol. 13 (1), pp. 17990. Date of Electronic Publication: 2023 Oct 20.
DOI: 10.1038/s41598-023-45160-w
Abstrakt: Innervation of the intestinal mucosa by the sympathetic nervous system is well described but the effects of adrenergic receptor stimulation on the intestinal epithelium remain equivocal. We therefore investigated the effect of sympathetic neuronal activation on intestinal cells in mouse models and organoid cultures, to identify the molecular routes involved. Using publicly available single-cell RNA sequencing datasets we show that the α 2A isoform is the most abundant adrenergic receptor in small intestinal epithelial cells. Stimulation of this receptor with norepinephrine or a synthetic specific α 2A receptor agonist promotes epithelial proliferation and stem cell function, while reducing differentiation in vivo and in intestinal organoids. In an anastomotic healing mouse model, adrenergic receptor α 2A stimulation resulted in improved anastomotic healing, while surgical sympathectomy augmented anastomotic leak. Furthermore, stimulation of this receptor led to profound changes in the microbial composition, likely because of altered epithelial antimicrobial peptide secretion. Thus, we established that adrenergic receptor α 2A is the molecular delegate of intestinal epithelial sympathetic activity controlling epithelial proliferation, differentiation, and host defense. Therefore, this receptor could serve as a newly identified molecular target to improve mucosal healing in intestinal inflammation and wounding.
(© 2023. Springer Nature Limited.)
Databáze: MEDLINE
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