WNT1-inducible signaling protein-1 induced by TGF-β1 contributes to fibrosis in Crohn’s disease

Liu, Shiqian (2023): WNT1-inducible signaling protein-1 induced by TGF-β1 contributes to fibrosis in Crohn’s disease. Dissertation, LMU München: Medizinische Fakultät

Abstract

Background: Intestinal fibrosis is a common and serious complication of Crohn’s disease (CD), oftentimes leading to intestinal obstruction and necessitating surgical intervention. The exact pathomechanisms are still incompletely understood, and no specific anti-fibrotic therapy for CD is currently available. Wnt-signaling components have been shown to play a significant role in fibrosis formation in other organs, however, their role in intestinal fibrosis formation is not fully known. Methods: Wnt signaling-specific qPCR arrays were used to analyze 84 Wnt-mediated signal transduction genes in fibrotic and non-fibrotic surgical specimen of patients with stricturing CD. Primary fibroblasts from a fibrotic section and non-fibrotic section were isolated. Cell proliferation and migration were measured by Ki-67 staining and wound healing assays. Cells were treated with TGF-β1 and WISP-1 for qPCR and functional analysis. Results: Several Wnt related genes were differentially expressed in fibrotic regions. A histopathological score showed a strong correlation between WISP-1 expression and fibrosis in fibrotic intestinal segments. Primary fibroblasts isolated from intestinal tissue of CD showed a significant difference in cell proliferation, migration, and ECM production between the fibrotic and control group. Stimulation of the cells with proinflammatory TGF-β1 induced the activation of Wnt signaling components and induced WISP-1 expression. The presence of WISP-1 induced migration but not proliferation of fibroblasts. Conclusions: Our results show that WISP-1 expression was associated with fibrosis formation in CD. According to this, WISP-1 might be a potential therapeutic target for attenuation of intestinal fibrosis in CD.

• Dokumententyp: Dissertationen (Dissertation, LMU München)
• Keywords: Crohn’s disease, intestinal fibrosis, WISP-1, Wnt, TGF-β1
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften ; 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• Fakultäten: Medizinische Fakultät
• Sprache der Hochschulschrift: Englisch
• Datum der mündlichen Prüfung: 12. Juli 2023
• 1. Bericht­erstatter:in: Friess, Helmut