Current Topics of the Mechanism of Intestinal Fibrosis in Crohn’s Disease

Honzawa, Yusuke; Yamamoto, Shuji; Okabe, Makoto; Seno, Hiroshi; Nakase, Hiroshi

doi:10.3390/immuno1040040

Cited by 2 publications

(2 citation statements)

References 68 publications

(101 reference statements)

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“…In the present animal experiment, we discovered that the colons from the DSS group tended to clearly shorten and thicken compared to those from the Normal group. Intestinal stricture in CD, developing as a result of fibrosis progression, which mainly occurs in the submucosa, is manifested by a thickening of the intestinal wall due to the hyperplasia of smooth muscle cells [ 77 ]. Likewise, the muscularis mucosae in the area of strictured intestine in UC was proven to be markedly thickened and linked with progressive fibrosis [ 78 ].…”

Section: Discussionmentioning

confidence: 99%

Therapeutic Potential of the Combination of Pentoxifylline and Vitamin-E in Inflammatory Bowel Disease: Inhibition of Intestinal Fibrosis

Lee

2022

JCM

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Background: Although intestinal fibrosis is a consequence of recurrent inflammation in Inflammatory bowel disease (IBD), alleviating inflammation alone does not prevent the progression of fibrosis, suggesting that the development of direct anti-fibrotic agents is necessary. This study aimed to evaluate the anti-fibrotic properties of combination treatment with pentoxifylline (PTX) and vitamin E (Vit-E) on human primary intestinal myofibroblasts (HIMFs) and the therapeutic potential of the combination therapy in murine models of IBD. Methods: HIMFs were pretreated with PTX, Vit-E, or both, and incubated with TGF-β1. We performed Western blot, qPCR, collagen staining, and immunofluorescence to estimate the anti-fibrotic effects of PTX and Vit-E. The cytotoxicity of these was investigated through MTT assay. To induce murine models of IBD for in vivo study, C57BL/6 mice were treated with repeated cycles of dextran sulfate sodium (DSS), developing chronic colitis. We examined whether the combined PTX and Vit-E treatment would effectively ameliorate colonic fibrosis in vivo. Results: We found that the co-treatment with PTX and Vit-E suppressed TGF-β1-induced expression of fibrogenic markers, with decreased expression of pERK, pSmad2, and pJNK, more than either treatment alone in HIMFs. Neither PTX nor Vit-E showed any significant cytotoxicity in given concentrations. Consistently with the in vitro results, the co-administration with PTX and Vit-E effectively attenuated colonic fibrosis with recovery from thickening and shortening of colon in murine models of IBD. Conclusions: These findings demonstrated that the combination of PTX and Vit-E exhibits significant anti-fibrotic effects in both HIMFs and in vivo IBD models, providing a promising therapy for IBD.

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Section: Discussionmentioning

confidence: 99%

Therapeutic Potential of the Combination of Pentoxifylline and Vitamin-E in Inflammatory Bowel Disease: Inhibition of Intestinal Fibrosis

Lee

2022

JCM

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“…Some highly innovative studies reported that, in RA, TGF-β is up-regulated by transglutaminase 2 (TG2), an enzyme that regulates ECM composition and degradation and, consequently, EMT through the activation of the transcription factors Snail/Slug, Twist, Zeb, and E47 [39]. In recent years, the activation of an EMT program related to fibrotic evolution has been demonstrated for various other autoimmune diseases, such as inflammatory bowel disease (IBD) [40], ulcerative colitis [41], and Crohn's disease [42]. Additionally, renal fibrosis features are often linked to SLE nephritis [43].…”

Section: Tgf-β Regulates Fibrosis Through the Activation Of Emtmentioning

confidence: 99%

Towards a Unified Approach in Autoimmune Fibrotic Signalling Pathways

Sisto

Lisi

2023

IJMS

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Autoimmunity is a chronic process resulting in inflammation, tissue damage, and subsequent tissue remodelling and organ fibrosis. In contrast to acute inflammatory reactions, pathogenic fibrosis typically results from the chronic inflammatory reactions characterizing autoimmune diseases. Despite having obvious aetiological and clinical outcome distinctions, most chronic autoimmune fibrotic disorders have in common a persistent and sustained production of growth factors, proteolytic enzymes, angiogenic factors, and fibrogenic cytokines, which together stimulate the deposition of connective tissue elements or epithelial to mesenchymal transformation (EMT) that progressively remodels and destroys normal tissue architecture leading to organ failure. Despite its enormous impact on human health, there are currently no approved treatments that directly target the molecular mechanisms of fibrosis. The primary goal of this review is to discuss the most recent identified mechanisms of chronic autoimmune diseases characterized by a fibrotic evolution with the aim to identify possible common and unique mechanisms of fibrogenesis that might be exploited in the development of effective antifibrotic therapies.

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Current Topics of the Mechanism of Intestinal Fibrosis in Crohn’s Disease

Cited by 2 publications

References 68 publications

Therapeutic Potential of the Combination of Pentoxifylline and Vitamin-E in Inflammatory Bowel Disease: Inhibition of Intestinal Fibrosis

Therapeutic Potential of the Combination of Pentoxifylline and Vitamin-E in Inflammatory Bowel Disease: Inhibition of Intestinal Fibrosis

Towards a Unified Approach in Autoimmune Fibrotic Signalling Pathways

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