Liu, Shiqian (2023): WNT1-inducible signaling protein-1 induced by TGF-β1 contributes to fibrosis in Crohn’s disease. Dissertation, LMU München: Faculty of Medicine |
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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.
Item Type: | Theses (Dissertation, LMU Munich) |
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Keywords: | Crohn’s disease, intestinal fibrosis, WISP-1, Wnt, TGF-β1 |
Subjects: | 600 Technology, Medicine 600 Technology, Medicine > 610 Medical sciences and medicine |
Faculties: | Faculty of Medicine |
Language: | English |
Date of oral examination: | 12. July 2023 |
1. Referee: | Friess, Helmut |
MD5 Checksum of the PDF-file: | 44e7267aa7b7953d297cd3e8d5e25a4d |
Signature of the printed copy: | 0700/UMD 21646 |
ID Code: | 32145 |
Deposited On: | 14. Mar 2024 10:51 |
Last Modified: | 14. Mar 2024 10:52 |