Angiotensinogen and transforming growth factor  1: novel genes in the pathogenesis of Crohn's disease

Hume, Georgia; Fowler, EV; Lincoln, Doug; Eri, Rajaraman; Templeton, David J; Florin, T.; Cavanaugh, J.A.; Radford-Smith, G.

doi:10.1136/jmg.2005.040477

Cited by 30 publications

(32 citation statements)

References 35 publications

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“…In these trials, ACE inhibitors and AT1 blockers have been considered as therapeutic agents. More recently, a clinical research report suggesting ANG II as a candidate therapeutic target to prevent strictures in CD has been published [49]. The present results, which demonstrate the potential contribution of ANG II to the stricture formation in CD, provide a theoretical basis for these projects.…”

Section: Discussionmentioning

confidence: 51%

Phenotypic change and accumulation of smooth muscle cells in strictures in Crohn’s disease: relevance to local angiotensin II system

et al. 2010

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Section: Discussionmentioning

confidence: 51%

Phenotypic change and accumulation of smooth muscle cells in strictures in Crohn’s disease: relevance to local angiotensin II system

et al. 2010

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“…Association with Crohn's disease-related intestinal strictures has been also reported for two SNPs (encoding V249I and T280M) in the gene coding for the receptor of CX3CL1 (CX3C chemokine ligand 1)/fractalkine [23,24] and variants of genes for TGFβ (transforming growth factor β), IL (interleukin)-10, IL-23 receptor, TLRs (Toll-like receptors), MMPs (matrix metalloproteinases) and TIMPs (tissue inhibitors of MMPs) [25,26].…”

Section: Genetic Basis Of Intestinal Fibrosismentioning

confidence: 91%

Pathogenic aspects and therapeutic avenues of intestinal fibrosis in Crohn's disease

2015

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In Crohn's disease, one of the two major forms of inflammatory bowel diseases in human beings, persistent and chronic inflammation promotes fibrotic processes thereby facilitating formation of strictures, the most common indication for surgical intervention in this disorder. The pathogenesis of Crohn's disease-associated fibrosis is not fully understood, but variants of genes involved in the recognition of microbial components/products [e.g. CARD15 (caspase-activating recruitment domain 15) and ATG16L1 (autophagy-related 16-like 1)] are associated with this phenotype, and experimental evidence suggests that intestinal fibrosis results from an altered balance between deposition of ECM (extracellular matrix) and degradation of ECM by proteases. Studies have also contributed to identify the main phenotypic and functional alterations of cells involved in the fibrogenic process, as well as molecules that stimulate such cells to produce elevated amounts of collagen and other ECM-related proteins. In the present review, we assess the current knowledge about cellular and molecular mediators of intestinal fibrosis and describe results of recent studies aimed at testing the preventive/therapeutic effect of compounds in experimental models of intestinal fibrosis.

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“…A recent Australian-based analysis of the angiotensinogen-6 variant found a significant association with Crohn's disease, also supporting the therapeutic potential for either angiotensin-converting enzyme inhibitors or angiotensin II receptor antagonists [44]. ACE inhibitors have had mixed results in animal models of colitis.…”

Section: Discussionmentioning

confidence: 99%

An angiotensin II receptor antagonist reduces inflammatory parameters in two models of colitis

Santiago

Rivera

Ferder

et al. 2008

Regulatory Peptides

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Little is known about the effects of the proinflammatory hormone Angiotensin II (Ang II) in inflammatory bowel disease. The aim of this study was to evaluate the effect of Valsartan (Diovan), an Ang II receptor antagonist, in two models of colitis.METHODS-Colitis was induced in Sprague-Dawley rats by administration of trinitrobenzene sulfonic acid (TNBS; 30mg in 50% ETOH ic) or 5% Dextran Sulphate Sodium (DSS) in drinking water ad libitum for 5 days. Valsartan was administered orally in drinking water (160mg/L) during thirty days prior to the induction of the colitis, and for 5 days after. All animals were evaluated for weight change, diarrhea, myeloperoxidase activity, macroscopic and microscopic damage. Cytokine levels in the colon were measured by ELISA, real time RT-PCR and immunohistochemistry.RESULTS-In the TNBS model, Valsartan reduced the macroscopic damage score, significantly decreased the microscopic damage (p<0.01), and accelerated weight gain after colitis. In the DSS colitis model, Valsartan treated animals had less diarrhea and microscopic damage. Valsartan reduced the protein levels of TGFβ (p<0.05), and IL-18 in the TNBS model, and led to over-expression of IL-10 mRNA in the DSS model.CONCLUSION-These data demonstrate a possible anti-inflammatory effect for Valsartan in colitis.

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Angiotensinogen and transforming growth factor 1: novel genes in the pathogenesis of Crohn's disease

Abstract: The association of the angiotensinogen-6 variant with Crohn's disease supports a potential role for angiotensin-converting enzyme inhibitors and angiotensin II receptor antagonists in disease treatment.

Cited by 30 publications

References 35 publications

Phenotypic change and accumulation of smooth muscle cells in strictures in Crohn’s disease: relevance to local angiotensin II system

Phenotypic change and accumulation of smooth muscle cells in strictures in Crohn’s disease: relevance to local angiotensin II system

Pathogenic aspects and therapeutic avenues of intestinal fibrosis in Crohn's disease

An angiotensin II receptor antagonist reduces inflammatory parameters in two models of colitis

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