Fibrogenesis in Crohn's Disease

Burke, John P.; Mulsow, Jürgen; O’Keane, Conor; Docherty, Neil G.; Watson, R. William G.; O'Connell, P. R.

doi:10.1111/j.1572-0241.2006.01010.x

Cited by 255 publications

(238 citation statements)

References 128 publications

(127 reference statements)

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“…34 Additionally, CB2 knockout mice are more sensitive than wild-type littermates to bleomycin-induced dermal fibrosis. 35 As > 30 % of patients with Crohn ' s disease develop intestinal fibrosis leading to stricture formation, frequently requiring surgical resection, 36 and myofibroblasts are key cells in the process of wound healing and stricture formation in the gut, 37 we investigated the in vitro effects of MAEA on myofibroblasts isolated from intestinal Crohn ' s disease strictures. We found that MAEA reduced collagen production by strictured Crohn ' s disease myofibroblasts and increased their migration ability, thus supporting the view that endocannabinoid pathways might be involved in the fibrogenic process in Crohn ' s disease.…”

Section: Articlesmentioning

confidence: 99%

The endogenous cannabinoid system in the gut of patients with inflammatory bowel disease

et al. 2011

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Activation of cannabinoid receptors (CBs) by endocannabinoids impacts on a number of gastrointestinal functions. Recent data indicate that CB1 agonists improve 2,4-dinitrobenzene sulfonic acid-induced colitis in mice, thus suggesting a role for the endocannabinoid agonist anandamide (AEA) in protecting the gut against inflammation. We here examined the gut endocannabinoid system in inflammatory bowel disease (IBD) patients, and investigated the ex vivo and in vitro effects of the non-hydrolysable AEA analog methanandamide (MAEA) on the mucosal proinflammatory response. The content of AEA, but not of 2-arachidonoyl-glycerol and N-palmitoylethanolamine, was significantly lower in inflamed than uninflamed IBD mucosa, and this was paralleled by lower activity of the AEA-synthesizing enzyme N-acyl-phosphatidylethanolamine-specific phospholipase D and higher activity of the AEA-degrading enzyme fatty acid amide hydrolase. MAEA significantly downregulated interferon-γ and tumor necrosis factor-α secretion by both organ culture biopsies and lamina propria mononuclear cells. Although these results are promising, further studies are needed to determine the role of cannabinoid pathways in gut inflammation.[...

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Section: Articlesmentioning

confidence: 99%

The endogenous cannabinoid system in the gut of patients with inflammatory bowel disease

et al. 2011

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“…Treatment associated with a reduction of the fraction of circulating CCR9-positive T cells producing interferon-γ or IL-17A, a subset of inflammatory T cells with gut-homing properties, which are increased in active CD [41,42]. Since TGF-β1 has pro-fibrogenic effects and CD natural history can be marked by the development of fibrostrictures [43], all the patients receiving Mongersen were monitored for the development of such a complication. No patient developed strictures or obstructive symptoms during the study nor had a significant increase in the serum levels of fibrogenic markers [44].…”

Section: Mongersen: the Clinical Relevance Of Smad7 Inhibitionmentioning

confidence: 99%

Smad7 as a Target for Immunomodulation Strategy in Inflammatory Bowel Diseases

Sedda¹,

Troncone²,

Imeneo³

et al. 2017

Immunome Res

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Inflammatory bowel diseases (IBD) are chronic inflammatory pathologies of the gut, characterized by a relapsingremitting course. Although IBD pathogenesis is not fully understood, epidemiological and experimental data suggest that multiple environmental factors can, in genetically predisposed individuals, trigger an excessive immune response directed against the antigens of the normal intestinal microflora, which eventually leads to the tissue damage. Defects in the physiological mechanisms/factors of counter-regulation contribute to amplify and sustain such a detrimental response. For instance, in inflamed tissue of IBD patients there is diminished activity of the immunesuppressive cytokine transforming growth factor (TGF)-β1, due to elevated levels of Smad7, an intracellular inhibitor of TGF-β1 signaling. Consistently, knockdown of Smad7 with a specific antisense oligonucleotide suppresses inflammatory signals in cultured intestinal cells of IBD patients and in the gut of mice with IBD-like experimental colitis. Moreover, treatment of patients with active Crohn's disease, one of the two major IBD in human beings, with Mongersen, an oral compound containing Smad7 antisense oligonucleotide, is accompanied by induction of clinical remission. Altogether these data indicate that targeting Smad7 represents a promising approach to modulate the ongoing mucosal inflammation in IBD.

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“…Some researchers have previously shown that inducible NO synthase (iNOS) expression was significantly elevated in STZ diabetic rat hearts [22] and once induced, iNOS is known to generate large amounts of NO until the enzyme is degraded [23]. Some cytokines, as example IGF-I, TGF-β1, connective tissue growth factor, platelet-derived growth factor, basic fibroblast growth factor, and epidermal growth factor, have been reported to both increase cellular proliferation (intestinal smooth muscle cells or myofibroblasts) and increase synthesis of ECM or collagen [24,25].…”

Section: Introductionmentioning

confidence: 99%

The Protective Effect of Resveratrol on Diabetic Cardiomyopathy

Karadeniz¹,

Muammer²

2018

Int J Diabetes Clin Res

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Based on the key role of hyperglycemia-caused oxidative stress in the formation of diabetic cardiomyopathy, increased antioxidant process would best restorative approach for control of diabetic cardiomyopathy. The increased nitrative stress and peroxynitrite, activation of iNOS and TGF-B1 play a crucial role in the pathogenesis of diabetic cardiomyopathy. Reduction of the expressions of the NOS-2 and TGF-B1 appears to be one of the important mechanisms for resveratrol effect on heart.

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Fibrogenesis in Crohn's Disease

Cited by 255 publications

References 128 publications

The endogenous cannabinoid system in the gut of patients with inflammatory bowel disease

The endogenous cannabinoid system in the gut of patients with inflammatory bowel disease

Smad7 as a Target for Immunomodulation Strategy in Inflammatory Bowel Diseases

The Protective Effect of Resveratrol on Diabetic Cardiomyopathy

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