Specific Differences in Migratory Function of Myofibroblasts Isolated from Crohn's Disease Fistulae and Strictures

Meier, Johannes K. -H. and Scharl, Michael and Miller, Sandra N. and Brenmoehl, Julia and Hausmann, Martin and Kellermeier, Silvia and Schoelmerich, Juergen and Rogler, Gerhard (2011) Specific Differences in Migratory Function of Myofibroblasts Isolated from Crohn's Disease Fistulae and Strictures. INFLAMMATORY BOWEL DISEASES, 17 (1). pp. 202-212. ISSN 1078-0998, 1536-4844

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Abstract

Background: Recently we found that migration of colonic lamina propria fibroblasts in Crohn's disease patients (CD-CLPF) from inflamed mucosa is significantly reduced as compared to control-CLPF. The behavior of CD-CLPFs isolated from fistulae and strictures was now investigated in detail. Methods: Initially migration assays for all CLPF cultures (CD-CLPF, fibrosis-CLPF, and fistula-CLPF) were performed in the modified 48-well Boyden chamber. Subsequently, for a migration assay more resembling the in vivo situation a 3D matrix model was developed. After seeding of cells into the 3D matrix the CLPF layer was wounded by an ERBIUM:YAG laser leading to circular cell rupture without effect on the extracellular matrix. Results: In the modified Boyden chamber migration of fistula-CLPF was significantly reduced compared to CD-CLPF. This was correlated with a decrease in FAK-protein expression, whereas in migrating fibrosis-CLPF an increase in FAK-protein expression, -autophosphorylation and migratory potential was found. This was confirmed in the 3D matrix wounding assay: Fistula-CLPF migrated less than CD-CLPF, whereas fibrosis-CLPF migrated significantly more in the 3D matrix wounding assay. Between 1 to 36 hours incubation time fibrosis-CLPF always displayed increased migration ability as compared to CD-CLPF. In contrast, fistula-CLPF migratory potential was always below that of CD-CLPF. Conclusions: Myofibroblasts isolated from inflamed, fibrostenotic, or fistulized CD mucosa differ in their migratory potential both in the modified Boyden chamber as well as in a 3D matrix model. These different migratory behaviors could be an explanation for impaired or excess wound healing and subsequently for fistula and fibrosis formation.

Item Type: Article
Uncontrolled Keywords: FOCAL ADHESION KINASE; INFLAMMATORY-BOWEL-DISEASE; CELL-MIGRATION; FIBROBLAST MIGRATION; FIBRONECTIN; INTERFERON; MECHANISMS; FAK; PATHOGENESIS; TGF-BETA-1; Crohn's disease; fibrosis; myofibroblasts; migration; focal adhesion kinase
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Innere Medizin I
Medicine > Lehrstuhl für Mund-, Kiefer- und Gesichtschirurgie
Depositing User: Dr. Gernot Deinzer
Date Deposited: 30 Jun 2020 10:27
Last Modified: 30 Jun 2020 10:27
URI: https://pred.uni-regensburg.de/id/eprint/21592

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