Antrum Mucosal Protein-18 Peptide Targets Tight Junctions to Protect and Heal Barrier Structure and Function in Models of Inflammatory Bowel Disease.
Inflamm Bowel Dis
; 21(10): 2393-2402, 2015 Oct.
Article
en En
| MEDLINE
| ID: mdl-26197453
ABSTRACT
BACKGROUND:
A peptide derived from Antrum Mucosal Protein (AMP)-18 (gastrokine-1) reduces the extent of mucosal erosions and clinical severity in mice with dextran sulfate sodium-induced colonic injury. This study set out to determine if AMP peptide was also therapeutic for immune- and cytokine-mediated mouse models of intestinal injury and inflammatory bowel diseases by enhancing and stabilizing tight junctions.METHODS:
Therapeutic effects of AMP peptide were examined in interleukin-10-deficient and a T-cell adoptive transfer models of colitis in immunodeficient recombinase activating gene-1 knock-out (RAG-1-/-) mice. Mechanisms by which AMP peptide enhances barrier function and structure were studied ex vivo using intestine and colon from mice given lipopolysaccharide and in AMP-18-deficient mice given dextran sulfate sodium.RESULTS:
In interleukin-10-deficient mice given piroxicam, AMP peptide enhanced recovery after weight loss, protected against colon shortening and segmental dilation, and reduced the colitis activity score. In the T-cell transfer model, treatment with the peptide protected against colon shortening. In mice given lipopolysaccharide in vivo to induce gut injury, AMP peptide prevented the onset of, and reversed established intestinal hyperpermeability by targeting TJ proteins and perijunctional actin. AMP-18-deficient mice challenged with dextran sulfate sodium exhibited increased mortality, developed erosions in the colon, and had lower levels of ZO-1 in TJs than heterozygous littermates or wild-type mice.CONCLUSIONS:
The results indicate that AMP-18/peptide may serve a protective role against injury along the gastrointestinal mucosal barrier, and recommend further development of AMP peptide as a novel agent to treat patients with inflammatory bowel disease.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Contexto en salud:
6_ODS3_enfermedades_notrasmisibles
Problema de salud:
6_digestive_diseases
Asunto principal:
Colitis
/
Colon
/
Uniones Estrechas
/
Hormonas Peptídicas
/
Proteínas de Uniones Estrechas
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Inflamm Bowel Dis
Asunto de la revista:
GASTROENTEROLOGIA
Año:
2015
Tipo del documento:
Article