Background and Aims: Although the mechanisms underlying the formation of intestinal fibrostrictures in Crohn's disease [CD] are not fully understood, activation of fibroblasts and excessive collagen deposition are supposed to contributeto the development of such complications. Here, we investigated the role of cadherin-11 [CDH-11], a fibroblast-derived protein that induces collagen production in various organs, in intestinal fibrosis.Methods: CDH-11 expression was evaluated in inflammatory [I] and fibrostricturing [FS] CD mucosal samples, ulcerative colitis [UC] mucosal samples, and deal and colonic control samples, by real-time polymerase chain reaction, western blotting, and immunohistochemistry. CDH-11 expression was evaluated in normal and in CD intestinal fibroblasts stimulated with inflammatory/fibrogenic cytokines. FS CD fibroblasts were cultured either with a specific CDH-11 antisense oligonucleotide [AS], or activating CDH-11 fusion protein and activation of RhoA/ROCK, andTGF-beta pathways and collagen production were evaluated by western blotting. Finally, we assessed the susceptibility of CDH-11-knockout [KO] mice to colitis-induced intestinal fibrosis.Results: CDH-11 RNA and protein expression were increased in both CD and UC as compared with controls. In CD, the greater expression of CDH-11 was seen in FS samples. Stimulation of fibroblasts with INF-ex, interleukin [IL]-6, IFN-gamma, IL-beta, and IL-1 beta enhanced CDH-11 expression. Knockdown of CDH-11 in FS CD fibroblasts impaired RhoA/ROCK/TGF-11 signalling and reduced collagen synthesis, whereas activation of CDH-11 increased collagen secretion. CDH-11 KO mice were largely protected from intestinal fibrosis.Conclusions: Data show that CDH-11 expression is up-regulated in inflammatory bowel disease [IBD] and suggest a role for this protein in the control of intestinal fibrosis.

Franzè, E., Monteleone, I., Laudisi, F., Rizzo, A., Dinallo, V., Di Fusco, D., et al. (2020). Cadherin-11 Is a Regulator of Intestinal Fibrosis. JOURNAL OF CROHN'S AND COLITIS, 14(3), 406-417 [10.1093/ecco-jcc/jjz147].

Cadherin-11 Is a Regulator of Intestinal Fibrosis

Monteleone, Ivan;Rizzo, Angelamaria;Dinallo, Vincenzo;Colantoni, Alfredo;Ortenzi, Angela;Di Carlo, Sara;Sica, Giuseppe;
2020-03-13

Abstract

Background and Aims: Although the mechanisms underlying the formation of intestinal fibrostrictures in Crohn's disease [CD] are not fully understood, activation of fibroblasts and excessive collagen deposition are supposed to contributeto the development of such complications. Here, we investigated the role of cadherin-11 [CDH-11], a fibroblast-derived protein that induces collagen production in various organs, in intestinal fibrosis.Methods: CDH-11 expression was evaluated in inflammatory [I] and fibrostricturing [FS] CD mucosal samples, ulcerative colitis [UC] mucosal samples, and deal and colonic control samples, by real-time polymerase chain reaction, western blotting, and immunohistochemistry. CDH-11 expression was evaluated in normal and in CD intestinal fibroblasts stimulated with inflammatory/fibrogenic cytokines. FS CD fibroblasts were cultured either with a specific CDH-11 antisense oligonucleotide [AS], or activating CDH-11 fusion protein and activation of RhoA/ROCK, andTGF-beta pathways and collagen production were evaluated by western blotting. Finally, we assessed the susceptibility of CDH-11-knockout [KO] mice to colitis-induced intestinal fibrosis.Results: CDH-11 RNA and protein expression were increased in both CD and UC as compared with controls. In CD, the greater expression of CDH-11 was seen in FS samples. Stimulation of fibroblasts with INF-ex, interleukin [IL]-6, IFN-gamma, IL-beta, and IL-1 beta enhanced CDH-11 expression. Knockdown of CDH-11 in FS CD fibroblasts impaired RhoA/ROCK/TGF-11 signalling and reduced collagen synthesis, whereas activation of CDH-11 increased collagen secretion. CDH-11 KO mice were largely protected from intestinal fibrosis.Conclusions: Data show that CDH-11 expression is up-regulated in inflammatory bowel disease [IBD] and suggest a role for this protein in the control of intestinal fibrosis.
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore MED/18
English
Con Impact Factor ISI
CDH-11
IBD
RhoA/ROCK pathway
TGF-β pathway
Franzè, E., Monteleone, I., Laudisi, F., Rizzo, A., Dinallo, V., Di Fusco, D., et al. (2020). Cadherin-11 Is a Regulator of Intestinal Fibrosis. JOURNAL OF CROHN'S AND COLITIS, 14(3), 406-417 [10.1093/ecco-jcc/jjz147].
Franzè, E; Monteleone, I; Laudisi, F; Rizzo, A; Dinallo, V; Di Fusco, D; Colantoni, A; Ortenzi, A; Giuffrida, P; Di Carlo, S; Sica, G; Di Sabatino, A; Monteleone, G
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/260851
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