MMP9 expression in intestinal fistula from patients with fistulizing CD and from human xenograft mouse model

Céline Mamie, Ramona S. Bruckner, Silvia Lang, Nahum Y. Shpigel, Matthias Turina, Andreas Rickenbacher, Daniela Cabalzar-Wondberg, Yolanda Chvatchko, Gerhard Rogler, Michael Scharl*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

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 in vivo studies investigating a possible therapeutic role for MMP-9 targeting as fistula therapy.

Original languageAmerican English
Article number1994350
JournalTissue Barriers
Volume10
Issue number2
DOIs
StatePublished - 2022

Bibliographical note

Publisher Copyright:
© 2021 Taylor & Francis Group, LLC.

Keywords

  • Crohn’s disease fistulas
  • MMP-9 (matrix metalloproteinase-9)
  • xenograft fistulas

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