Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-47034
Meier, J K H; Scharl, M; Miller, S N; Brenmoehl, J; Hausmann, M; Kellermeier, S; Schölmerich, J; Rogler, G (2011). Specific differences in migratory function of myofibroblasts isolated from Crohn's disease fistulae and strictures. Inflammatory Bowel Diseases, 17(1):202-212.
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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.
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|Item Type:||Journal Article, refereed, original work|
|Communities & Collections:||04 Faculty of Medicine > University Hospital Zurich > Clinic for Gastroenterology and Hepatology|
|DDC:||610 Medicine & health|
|Deposited On:||07 Mar 2011 15:49|
|Last Modified:||27 Nov 2013 16:27|
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