An anti-eCIRP strategy for necrotizing enterocolitis.
Inflammation
MFG-E8
MOP3
Necrotizing enterocolitis
eCIRP
Journal
Molecular medicine (Cambridge, Mass.)
ISSN: 1528-3658
Titre abrégé: Mol Med
Pays: England
ID NLM: 9501023
Informations de publication
Date de publication:
20 Sep 2024
20 Sep 2024
Historique:
received:
20
05
2024
accepted:
11
09
2024
medline:
21
9
2024
pubmed:
21
9
2024
entrez:
20
9
2024
Statut:
epublish
Résumé
Necrotizing enterocolitis (NEC) is a severe gastrointestinal disease characterized by intestinal inflammation and injury, with high mortality risk. Extracellular cold-inducible RNA-binding protein (eCIRP) is a recently discovered damage-associated molecular pattern that propagates inflammation and tissue injury; however, the role of eCIRP in NEC remains unknown. We hypothesize that eCIRP exacerbates NEC pathogenesis and the novel eCIRP-scavenging peptide, milk fat globule-epidermal growth factor-factor VIII (MFG-E8)-derived oligopeptide 3 (MOP3), attenuates NEC severity, serving as a new therapeutic strategy to treat NEC. Stool samples from premature neonates were collected prospectively and eCIRP levels were measured. Wild-type (WT) and CIRP Stool samples from NEC neonates had elevated eCIRP levels compared to healthy age-matched controls (p < 0.05). CIRP eCIRP exacerbates NEC evidenced by protection with CIRP-deficiency and administration of MOP3, a CIRP-directed therapeutic, in a murine model. Thus, eCIRP is a novel target with human relevance, and MOP3 is a promising treatment for lethal NEC.
Sections du résumé
BACKGROUND
BACKGROUND
Necrotizing enterocolitis (NEC) is a severe gastrointestinal disease characterized by intestinal inflammation and injury, with high mortality risk. Extracellular cold-inducible RNA-binding protein (eCIRP) is a recently discovered damage-associated molecular pattern that propagates inflammation and tissue injury; however, the role of eCIRP in NEC remains unknown. We hypothesize that eCIRP exacerbates NEC pathogenesis and the novel eCIRP-scavenging peptide, milk fat globule-epidermal growth factor-factor VIII (MFG-E8)-derived oligopeptide 3 (MOP3), attenuates NEC severity, serving as a new therapeutic strategy to treat NEC.
METHODS
METHODS
Stool samples from premature neonates were collected prospectively and eCIRP levels were measured. Wild-type (WT) and CIRP
RESULTS
RESULTS
Stool samples from NEC neonates had elevated eCIRP levels compared to healthy age-matched controls (p < 0.05). CIRP
CONCLUSIONS
CONCLUSIONS
eCIRP exacerbates NEC evidenced by protection with CIRP-deficiency and administration of MOP3, a CIRP-directed therapeutic, in a murine model. Thus, eCIRP is a novel target with human relevance, and MOP3 is a promising treatment for lethal NEC.
Identifiants
pubmed: 39304832
doi: 10.1186/s10020-024-00935-3
pii: 10.1186/s10020-024-00935-3
doi:
Substances chimiques
RNA-Binding Proteins
0
Cirbp protein, mouse
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
156Subventions
Organisme : Foundation for the National Institutes of Health
ID : R01GM129633
Organisme : Foundation for the National Institutes of Health
ID : U01AI170018
Organisme : Foundation for the National Institutes of Health
ID : R35GM118337
Organisme : Foundation for the National Institutes of Health
ID : R01HL076179
Organisme : Foundation for the National Institutes of Health
ID : R01AA028947
Organisme : Foundation for the National Institutes of Health
ID : U01AI170018
Informations de copyright
© 2024. The Author(s).
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