A critical role for erythropoietin on vagus nerve Schwann cells in intestinal motility.
Enteric glial cells
Erythropoietin
Erythropoietin receptors knockout
Intestinal manipulation
Intestinal transit time
Postoperative ileus.
Schwann cells
Structural analysis
Vagus nerve
Journal
BMC biotechnology
ISSN: 1472-6750
Titre abrégé: BMC Biotechnol
Pays: England
ID NLM: 101088663
Informations de publication
Date de publication:
01 05 2023
01 05 2023
Historique:
received:
25
01
2023
accepted:
30
03
2023
medline:
3
5
2023
pubmed:
2
5
2023
entrez:
1
5
2023
Statut:
epublish
Résumé
Dysmotility and postoperative ileus (POI) are frequent major clinical problems post-abdominal surgery. Erythropoietin (EPO) is a multifunctional tissue-protective cytokine that promotes recovery of the intestine in various injury models. While EPO receptors (EPOR) are present in vagal Schwann cells, the role of EPOR in POI recovery is unknown because of the lack of EPOR antagonists or Schwann-cell specific EPOR knockout animals. This study was designed to explore the effect of EPO via EPOR in vagal nerve Schwann cells in a mouse model of POI. The structural features of EPOR and its activation by EPO-mediated dimerization were understood using structural analysis. Later, using the Cre-loxP system, we developed a myelin protein zero (Mpz) promoter-driven knockout mouse model of Schwann cell EPOR (MpzCre-EPOR To the best of our knowledge, this is the first pre-clinical study to demonstrate a novel mouse model of EPOR specific knock out on Schwan cells with an effect in the gut. We also showed novel beneficial effects of EPO through vagus nerve Schwann cell-EPOR in intestinal dysmotility. Our findings suggest that EPO-EPOR signaling in the vagus nerve after POI is important for the functional recovery of ITT.
Sections du résumé
BACKGROUND
Dysmotility and postoperative ileus (POI) are frequent major clinical problems post-abdominal surgery. Erythropoietin (EPO) is a multifunctional tissue-protective cytokine that promotes recovery of the intestine in various injury models. While EPO receptors (EPOR) are present in vagal Schwann cells, the role of EPOR in POI recovery is unknown because of the lack of EPOR antagonists or Schwann-cell specific EPOR knockout animals. This study was designed to explore the effect of EPO via EPOR in vagal nerve Schwann cells in a mouse model of POI.
RESULTS
The structural features of EPOR and its activation by EPO-mediated dimerization were understood using structural analysis. Later, using the Cre-loxP system, we developed a myelin protein zero (Mpz) promoter-driven knockout mouse model of Schwann cell EPOR (MpzCre-EPOR
CONCLUSIONS
To the best of our knowledge, this is the first pre-clinical study to demonstrate a novel mouse model of EPOR specific knock out on Schwan cells with an effect in the gut. We also showed novel beneficial effects of EPO through vagus nerve Schwann cell-EPOR in intestinal dysmotility. Our findings suggest that EPO-EPOR signaling in the vagus nerve after POI is important for the functional recovery of ITT.
Identifiants
pubmed: 37127673
doi: 10.1186/s12896-023-00781-x
pii: 10.1186/s12896-023-00781-x
pmc: PMC10152589
doi:
Substances chimiques
Receptors, Erythropoietin
0
Erythropoietin
11096-26-7
Types de publication
Journal Article
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
12Subventions
Organisme : NIAMS NIH HHS
ID : K08 AR060164
Pays : United States
Informations de copyright
© 2023. The Author(s).
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