The V249I polymorphism of the CX3CR1 gene is associated with fibrostenotic disease behavior in patients with Crohnʼs disease

Sabaté, Jean‐Marc; Ameziane, Nejma; Lamoril, J.; Jouët, Pauline; Farmachidi, Jean-Pierre; Soulé, Jean–Claude; Harnois, Florence; Sobhani, Iradj; Jian, Raymond; Deybach, Jean‐Charles; Prost, Dominique de; Coffin, Benoït

doi:10.1097/meg.0b013e3282f824c9

Cited by 39 publications

(39 citation statements)

References 51 publications

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“…ECM is produced by activated myofibroblasts that are regulated by profibrotic and antifibrotic factors [9]. The main components of ECM are collagen and fibronectin [27]. In addition, α-SMA is another major constituent of ECM.…”

Section: Discussionmentioning

confidence: 99%

Calycosin Inhibits Intestinal Fibrosis on CCD-18Co Cells via Modulating Transforming Growth Factor-β/Smad Signaling Pathway

et al. 2019

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Background: Intestinal fibrosis is the major complication of Crohn’s disease (CD). There are no other good treatments for CD except surgery and remains a refractory disease. Calycosin (CA), the active component of astragalus membranaceus, has been reported the potential effect on lung fibrosis and renal fibrosis. In this study, we aim to explore the effect of CA on intestinal fibrosis in vitro and the possible signal pathway. Methods: The antifibrotic effect of CA is investigated in human intestinal fibroblasts (CCD-18Co) cells induced by transforming growth factor-β1 (TGF-β1). MTT method was used to screen the concentration of CA. Real-time polymerase chain reaction and western blot analysis were used to evaluate the expression of α-smooth muscle actin (α-SMA), collagen I, and TGF-β/Smad pathway. Results: The results showed that the concentration of CA was 12.5, 25, 50 μmol/L. CA could inhibit the expression of α-SMA and collagen I. In addition, CA regulated the expression of TGF-β/Smad signaling pathway. Conclusion: This study demonstrated that CA could inhibit the activation of CCD-18Co cells and reduce the expression of extracellular matrix. Our study highlighted that CA-inhibited TGF-β/Smad pathway through inhibiting the expression of p-Smad2, p-Smad3, Smad4, and TGF-β1 and raised the Smad7 expression. Therefore, CA might inhibit intestinal fibrosis by inhibiting the TGF-β/Smad pathway.

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Section: Discussionmentioning

confidence: 99%

Calycosin Inhibits Intestinal Fibrosis on CCD-18Co Cells via Modulating Transforming Growth Factor-β/Smad Signaling Pathway

et al. 2019

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“…In this study, T280M homozygous genotype was observed in three patients, with two of them having been diagnosed with stenosis. V249I polymorphism was detected in patients with fi brostenosis [13].…”

Section: Discussionmentioning

confidence: 97%

“…Th ese polymorphisms are implicated in atherosclerosis, coronary artery disease, and susceptibility to HIV  infection. Th ey also infl uence CD phenotype and localization [11][12][13].…”

Section: Introductionmentioning

confidence: 99%

Fractalkine receptor polymorphism may not be associated with the development and clinical course of ulcerative colitis

Gökcan¹,

Yurtçu

Şelçuk

et al. 2015

Biomol Biomed

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Fractalkine (CX3C), a chemokine expressed by epithelial cells within normal and infl amed colorectal mucosa, induces leukocyte adhesion and migration via fractalkine receptor. Th e aim of this study was to investigate two single nucleotide polymorphisms of the fractalkine receptor gene as a risk factor both for the development and clinical fi ndings of ulcerative colitis. In this study, 51 patients with ulcerative colitis (UC) and 80 controls were recruited. Genotypes of fractalkine receptorc.745G>A (V249I) and c.839C>T (T280M) polymorphisms were identifi ed by restriction fragment length polymorphism analyses after polymerase chain reaction.Genotype distribution and allele frequencies of V249I and T280M were not statistically signifi cantly diff erent between UC and control groups (p>0.05). No statistically signifi cant relationship was found between fractalkine receptor polymorphisms and clinical fi ndings of UC. We observed no signifi cant diff erence in fractalkine receptor polymorphism between patients and control group and no genotype-phenotype relation. Th erefore, we concluded that fractalkine receptor polymorphisms may not contribute to the molecular pathogenesis of UC.

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“…13 T280M and V249I polymorphisms of the chemokine fractalkine receptor CX3CR1 influence the stricturing phenotype, regardless of NOD2 status. 14,15 The 5T5T genotype at the MMP-3 SNP-1613 5 T/6 T increases the percentage of stenotic complications through an unbalanced tissue remodelling, but prevents colonic involvement in Crohn's disease. 16 Crohn's disease fibrosis is also associated with variants in the autophagy-related-16L1 gene (rs2241879 and rs2241880), implicated in autophagy and bacterial phagocytosis, and in the IL23 receptor gene (TT genotype of rs1004819).…”

Section: Genesmentioning

confidence: 99%

Biomarkers of intestinal fibrosis – one step towards clinical trials for stricturing inflammatory bowel disease

Giuffrida

Pinzani

Corazza

et al. 2016

United European Gastroenterology Journal

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Intestinal fibrosis, caused by an excessive deposition of extracellular matrix components, and subsequent stricture development are a common complication of inflammatory bowel disease. However, currently there are no biomarkers which reliably predict the risk of developing intestinal strictures or identify early stages of fibrosis prior to clinical symptoms. Candidate biomarkers of intestinal fibrosis, including gene variants (i.e. nucleotide-binding oligomerization domain-2 gene), serum microRNAs (miR-19, miR-29), serum extracellular matrix proteins (i.e. collagen, fibronectin) or enzymes (i.e. tissue inhibitor of matrix metalloproteinase-1), serum growth factors (i.e. basic fibroblast growth factor, YKL-40), serum anti-microbial antibodies (i.e. anti-Saccharomyces cerevisiae) and circulating cells (i.e. fibrocytes) have shown conflicting results on relatively heterogeneous patients' cohorts, and none of them was proven to be strictly specific for fibrostenosis, but rather predictive of a disease disabling course. In this review we critically reassess the diagnostic and prognostic value of serum biomarkers of intestinal fibrosis in inflammatory bowel disease.

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The V249I polymorphism of the CX3CR1 gene is associated with fibrostenotic disease behavior in patients with Crohnʼs disease

Abstract: In Crohn's disease, V249I CX3CR1 polymorphism is associated with intestinal strictures, particularly in smokers. This association is independent of CARD15 mutations.

Cited by 39 publications

References 51 publications

Calycosin Inhibits Intestinal Fibrosis on CCD-18Co Cells via Modulating Transforming Growth Factor-β/Smad Signaling Pathway

Calycosin Inhibits Intestinal Fibrosis on CCD-18Co Cells via Modulating Transforming Growth Factor-β/Smad Signaling Pathway

Fractalkine receptor polymorphism may not be associated with the development and clinical course of ulcerative colitis

Biomarkers of intestinal fibrosis – one step towards clinical trials for stricturing inflammatory bowel disease

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