Vasoactive intestinal peptide promotes secretory differentiation and mitigates radiation-induced intestinal injury

Tatiana Agibalova; Anneke Hempel; H. Carlo Maurer; Mohab Ragab; Anastasia Ermolova; Jessica Wieland; Caroline Waldherr Ávila de Melo; Fabian Heindl; Maximilian Giller; Julius Clemens Fischer; Markus Tschurtschenthaler; Birgit Kohnke-Ertel; Rupert Öllinger; Katja Steiger; Ihsan Ekin Demir; Dieter Saur; Michael Quante; Roland M. Schmid; Moritz Middelhoff

doi:10.1186/s13287-024-03958-z

Stem Cell Research & Therapy (Oct 2024)

Vasoactive intestinal peptide promotes secretory differentiation and mitigates radiation-induced intestinal injury

Tatiana Agibalova,
Anneke Hempel,
H. Carlo Maurer,
Mohab Ragab,
Anastasia Ermolova,
Jessica Wieland,
Caroline Waldherr Ávila de Melo,
Fabian Heindl,
Maximilian Giller,
Julius Clemens Fischer,
Markus Tschurtschenthaler,
Birgit Kohnke-Ertel,
Rupert Öllinger,
Katja Steiger,
Ihsan Ekin Demir,
Dieter Saur,
Michael Quante,
Roland M. Schmid,
Moritz Middelhoff

Affiliations

Tatiana Agibalova: Department of Internal Medicine II, Klinikum rechts der Isar, TUM School of Medicine and Health, Technical University of Munich
Anneke Hempel: Department of Internal Medicine II, Klinikum rechts der Isar, TUM School of Medicine and Health, Technical University of Munich
H. Carlo Maurer: Department of Internal Medicine II, Klinikum rechts der Isar, TUM School of Medicine and Health, Technical University of Munich
Mohab Ragab: Department of Internal Medicine II, Klinikum rechts der Isar, TUM School of Medicine and Health, Technical University of Munich
Anastasia Ermolova: Department of Internal Medicine II, Klinikum rechts der Isar, TUM School of Medicine and Health, Technical University of Munich
Jessica Wieland: Department of Internal Medicine II, Klinikum rechts der Isar, TUM School of Medicine and Health, Technical University of Munich
Caroline Waldherr Ávila de Melo: Department of Internal Medicine II, Klinikum rechts der Isar, TUM School of Medicine and Health, Technical University of Munich
Fabian Heindl: Department of Internal Medicine II, Klinikum rechts der Isar, TUM School of Medicine and Health, Technical University of Munich
Maximilian Giller: Department of Radiation Oncology, Klinikum rechts der Isar, TUM School of Medicine and Health, Technical University of Munich
Julius Clemens Fischer: Department of Radiation Oncology, Klinikum rechts der Isar, TUM School of Medicine and Health, Technical University of Munich
Markus Tschurtschenthaler: Division of Translational Cancer Research, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK)
Birgit Kohnke-Ertel: Department of Internal Medicine II, Klinikum rechts der Isar, TUM School of Medicine and Health, Technical University of Munich
Rupert Öllinger: Institute of Molecular Oncology and Functional Genomics, Center for Translational Cancer Research (TranslaTUM), TUM School of Medicine and Health, Technical University of Munich
Katja Steiger: Institute of Pathology, TUM School of Medicine and Health, Technical University of Munich
Ihsan Ekin Demir: Department of Surgery, Klinikum rechts der Isar, TUM School of Medicine and Health, Technical University of Munich
Dieter Saur: Division of Translational Cancer Research, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK)
Michael Quante: Department of Internal Medicine II, Faculty of Medicine, Freiburg University Medical Center, University of Freiburg
Roland M. Schmid: Department of Internal Medicine II, Klinikum rechts der Isar, TUM School of Medicine and Health, Technical University of Munich
Moritz Middelhoff: Department of Internal Medicine II, Klinikum rechts der Isar, TUM School of Medicine and Health, Technical University of Munich

DOI: https://doi.org/10.1186/s13287-024-03958-z
Journal volume & issue: Vol. 15, no. 1
pp. 1 – 14

Abstract

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Abstract Background Vasoactive intestinal peptide (VIP) is a neuronal peptide with prominent distribution along the enteric nervous system. While effects of VIP on intestinal motility, mucosal vasodilation, secretion, and mucosal immune cell function are well-studied, the direct impact of VIP on intestinal epithelial cell turnover and differentiation remains less understood. Intestinal stem and progenitor cells are essential for the maintenance of intestinal homeostasis and regeneration, and their functions can be modulated by factors of the stem cell niche, including neuronal mediators. Here, we investigated the role of VIP in regulating intestinal epithelial homeostasis and regeneration following irradiation-induced injury. Methods Jejunal organoids were derived from male and female C57Bl6/J, Lgr5-EGFP-IRES-CreERT2 or Lgr5-EGFP-IRES-CreERT2/R26R-LSL-TdTomato mice and treated with VIP prior to analysis. Injury conditions were induced by exposing organoids to 6 Gy of irradiation (IR). To investigate protective effects of VIP in vivo, mice received 12 Gy of abdominal IR followed by intraperitoneal injections of VIP. Results We observed that VIP promotes epithelial differentiation towards a secretory phenotype predominantly via the p38 MAPK pathway. Moreover, VIP prominently modulated epithelial proliferation as well as the number and proliferative activity of Lgr5-EGFP+ progenitor cells under homeostatic conditions. In the context of acute irradiation injury in vitro, we observed that IR injury renders Lgr5-EGFP+ progenitor cells more susceptible to VIP-induced modulations, which coincided with the strong promotion of epithelial regeneration by VIP. Finally, the observed effects translate into an in vivo model of abdominal irradiation, where VIP showed to prominently mitigate radiation-induced injury. Conclusions VIP prominently governs intestinal homeostasis by regulating epithelial progenitor cell proliferation and differentiation and promotes intestinal regeneration following acute irradiation injury.

Published in Stem Cell Research & Therapy

ISSN: 1757-6512 (Online)
Publisher: BMC
Country of publisher: United Kingdom
LCC subjects: Medicine: Medicine (General); Science: Chemistry: Organic chemistry: Biochemistry
Website: https://stemcellres.biomedcentral.com

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