Transforming growth factor-βs and their signaling receptors are coexpressed in Crohn's disease

Fabio F. Di Mola, Helmut Friess, Axel Scheuren, Pierluigi Di Sebastiano, Hans Graber, Bernhard Egger, Arthur Zimmermann, Murray Korc, Markus W. Büchler

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60 Scopus citations

Abstract

Objective: To evaluate mechanisms that contribute to tissue repair and tissue remodeling in Crohn's disease (CD). Summary Background Data: Transforming growth factor-βs (TGF-βs) are involved in different chronic inflammatory disorders. They function by binding to two receptors, type I (TβR-I) subtype ALK5 and type II (TβR-II), which are concomitantly required for signal transduction. Methods: Tissues were obtained from 18 patients with CD (10 female patients, 8 male patients, median age 38.7 years [range 16 to 58 years]) undergoing surgery because of CD-related complications. Tissue samples of 18 healthy organ donors (10 female subjects, 8 male subjects, median age 50.3 years [range 15 to 65 years]) served as controls. The expression and localization of TGF-β1, TGF-β2, TGF-β3, TβR-I(ALKS), TβR- II, and TβR-III were studied by Northern blot analysis, in situ hybridization, and immunohistochemistry. Results: On Northern blot analysis, 94% of the CD samples exhibited enhanced TGF-β1, TGF-β3, and TβR-II mRNA expression compared with controls. TGF-β2 was increased in 72%, TβR-I(ALK5) in 72%, and TβR-III in 82% of the patients with CD. On in situ hybridization and immunohistochemical analysis, TGFβ1, TβR-I(ALK5), and Tβ-II were seen to be colocalized in the lamina propria cells and in the lymphocytes closest to the luminal surface, but also in the remaining epithelial cells, and in fibroblasts of CD tissue samples. Conclusions: The concomitant overexpression of TGF-βs and their signaling receptors in CD points to a potential role of these regulatory molecules in the pathophysiology of CD. Activation of TGF- β-mediated pathways might promote the repair of mucosal injury by enhancing the process of reepithelization, but might also contribute to extracellular matrix generation and subsequently to intramural fibrosis and intestinal obstruction.

Original languageEnglish (US)
Pages (from-to)67-75
Number of pages9
JournalAnnals of surgery
Volume229
Issue number1
DOIs
StatePublished - Jan 1 1999

ASJC Scopus subject areas

  • Surgery

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    Di Mola, F. F., Friess, H., Scheuren, A., Di Sebastiano, P., Graber, H., Egger, B., Zimmermann, A., Korc, M., & Büchler, M. W. (1999). Transforming growth factor-βs and their signaling receptors are coexpressed in Crohn's disease. Annals of surgery, 229(1), 67-75. https://doi.org/10.1097/00000658-199901000-00009