MMP9 expression in intestinal fistula from patients with fistulizing CD and from human xenograft mouse model.
Crohn’s disease fistulas
MMP-9 (matrix metalloproteinase-9)
xenograft fistulas
Journal
Tissue barriers
ISSN: 2168-8370
Titre abrégé: Tissue Barriers
Pays: United States
ID NLM: 101601065
Informations de publication
Date de publication:
03 04 2022
03 04 2022
Historique:
pubmed:
29
10
2021
medline:
3
5
2022
entrez:
28
10
2021
Statut:
ppublish
Résumé
Fistula treatment represents a major unmet medical need in the therapy of Crohn's disease (CD). Current medical therapies, such as anti-TNF antibody treatments, are often insufficient and do not achieve permanent fistula closure. Previously published data point toward a critical role for metalloproteinase-9 (MMP-9)/gelatinase B in fistula pathogenesis. The aim of this project was to investigate in detail MMP-9 expression in different fistula types and to confirm that MMP-9 is a potential target for fistula therapy in CD patients.Immunohistochemistry for total and active MMP-9, Cytokeratin 8 (CK-8) and co-staining of active MMP-9/CK-8 was performed in specimen derived from perianal fistulas, entero-enteric fistulas and fistulas from patients not responding to anti-TNF therapy. In addition, fistulas from the xenograft mouse model (anti-TNF treated or untreated) were analyzed.Total and active MMP-9 protein was detectable in cells lining the tracts of perianal and entero-enteric fistulas. Of note, total and active MMP-9 was also expressed in fistulas of CD patients non-responding to anti-TNF treatment. Interestingly, we detected considerable co-staining of active MMP-9 and CK-8 in particular in cells lining the fistula tract and in transitional cells around the fistulas. Furthermore, total and active MMP-9 are detectable in both anti-TNF treated and untreated xenograft fistulas.Taken together, our data suggest that MMP-9 is involved in fistula pathogenesis in CD patients, in fistulas of different origins and particularly in patients non-responding to anti-TNF therapy. Our xenograft fistula model is suitable for
Identifiants
pubmed: 34709129
doi: 10.1080/21688370.2021.1994350
pmc: PMC9067458
doi:
Substances chimiques
Tumor Necrosis Factor Inhibitors
0
MMP9 protein, human
EC 3.4.24.35
Matrix Metalloproteinase 9
EC 3.4.24.35
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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