Laura Gisbert Ferrándiz

Laura Gisbert Ferrándiz
University of Valencia | UV · Department of Pharmacology

PhD

About

33
Publications
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155
Citations

Publications

Publications (33)
Article
Full-text available
Background: Fibrosis is a common complication of Crohn's disease (CD) in which macrophages play a central role. Epithelial-mesenchymal transition (EMT) and the WNT pathway have been associated with fibrosis. We aim to analyse the relevance of the tissue microenvironment in macrophage phenotype and the EMT process. Methods: Intestinal surgical re...
Article
Full-text available
Intestinal epithelial cells (IECs) constitute a defensive physical barrier in mucosal tissues and their disruption is involved in the etiopathogenesis of several inflammatory pathologies, such as Ulcerative Colitis (UC). Recently, the succinate receptor SUCNR1 was associated with the activation of inflammatory pathways in several cell types, but li...
Article
Background Crohn′s disease (CD) is often complicated by the appearance of intestinal stenosis (B2 behaviour) or fistulas (B3 behaviour), and the factors determining the pattern of disease and the etiology of these lesions, both associated with fibrosis and requiring surgery, are poorly defined. Our aim has been to detect transcriptomic alterations...
Article
Background Fibrosis is a complication commonly present in Crohn’s disease (CD) patients with a structuring (B2) or penetrating (B3) phenotype, with no effective treatment. This process is characterized by a disequilibrium between the production and degradation of the extracellular matrix (ECM), mainly regulated by myofibroblasts. We aim to analyse...
Article
Background Fibrosis constitute the main complications associated to Crohn’s disease (CD). Notch signalling has been implicated in lung, kidney, liver and cardiac fibrosis. Macrophages contribute to fibrosis through the release of different mediators and the pattern of secretion may vary according to their microenvironment. The aim of the present st...
Article
Background Ulcerative colitis (UC) is characterized by a diffuse, continuous, and chronic inflammation of mucosa and submucosa layers in the colon1. Inflammasome complex is involved in the intestinal homeostasis regulation, but its role in UC has not been established yet. We have recently reported that SUCNR1 mediates intestinal inflammation and fi...
Article
Background Crohn’s disease (CD) is a chronic inflammatory disorder of the gastrointestinal tract whose etiology is unknown. CD is associated with complications such as fibrosis or fistula, which cannot be pharmacologically reversed, requiring repeated surgery. Although a profibrotic effect of the P2X7 receptor has been described in some scenarios s...
Article
Background The Krebs cycle metabolite succinate contributes to inflammatory conditions like arthritis and colitis by activating its receptor SUCNR1. We aimed to analyze whether the succinate-SUCNR1 pathway contributes to the leukocyte-endothelial cell interactions that initiate the inflammatory response. Methods We evaluated leukocyte rolling and...
Article
Background Crohn’s Disease (CD) patients often develop stenotic complications as immunomodulatory treatments do not prevent the fibrogenic response in the affected tissues, where a dysregulated activation of stromal cells provokes an excessive deposition of extracellular matrix (ECM). Recent evidences support the notion that local cells can sense t...
Article
Background Vitamin D receptor (VDR) is a member of the nuclear receptor family of transcription factors that plays an immunomodulatory role in the gastrointestinal tract through binding Vitamin D. Single-nucleotide polymorphisms (SNPs) in the VDR gene have been related to inflammatory bowel disease. Indeed, Crohn′s disease (CD) patients carrying th...
Article
Full-text available
Inflammatory bowel disease (IBD) is a relapsing chronic disorder of the gastrointestinal tract characterized by disruption of epithelial barrier function and excessive immune response to gut microbiota. The lack of biomarkers providing early diagnosis or defining the status of the pathology difficulties an accurate assessment of the disease. Given...
Article
The synonymous single nucleotide polymorphism (SNP) rs731236, located in the vitamin D receptor (VDR) gene (Taq I) has been associated with both decreased levels of the protein in peripheral blood mononuclear cells and a fibrosis-related complication in Crohn´s disease (CD). Interactions between VDR and a protein-disulfide isomerase-associated 3 (P...
Article
Full-text available
The pathogenesis of Crohn’s disease-associated fibrostenosis and fistulas imply the epithelial-to-mesenchymal transition (EMT) process. As succinate and its receptor (SUCNR1) are involved in intestinal inflammation and fibrosis, we investigated their relevance in EMT and Crohn’s disease (CD) fistulas. Succinate levels and SUCNR1-expression were ana...
Article
Full-text available
Vitamin D (VD) deficiency has been associated to Crohn’s disease (CD) pathogenesis, and the exogenous administration of VD improves the course of the disease, but the mechanistic basis of these observations remains unknown. Vitamin D receptor (VDR) mediates most of the biological functions of this hormone, and we aim to analyze here the expression...
Article
Background Intestinal fistula is a common complication in CD patients whose aetiology is still not well-characterised. It is associated with an exacerbated inflammation and epithelial-to-mesenchymal transition (EMT), a process which allows a switch from epithelial towards a fibrotic behaviour. We have recently reported that SUCNR1 mediates intestin...
Article
Background Fibrosis is a common complication in Crohn’s disease (CD) patients and fibroblasts play an important role in the fibrogenic process. Low vitamin D (VD) levels and a defective VD-signalling pathway have been reported in CD. VD signals through both vitamin D receptor (VDR) and protein disulfide-isomerase A3 (PDIA3) and we have previously d...
Article
Full-text available
We recently observed reduced autophagy in Crohn’s disease patients and an anti-inflammatory effect of autophagy stimulation in murine colitis, but both anti- and pro-fibrotic effects are associated with autophagy stimulation in different tissues, and fibrosis is a frequent complication of Crohn’s disease. Thus, we analyzed the effects of pharmacolo...
Article
Full-text available
Background and Aims Epithelial-mesenchymal transition (EMT) has been related to fibrosis and fistula formation, common complications associated to Crohn´s disease (CD). The WNT signaling pathway mediates EMT and specific WNT/FZD interactions have been related with the activation of this process in several diseases. We aim to analyze the relevance o...
Article
Background Macrophages contribute to fibrosis through the release of different mediators and the pattern of secretion may vary according to their phenotype. The expression of WNT ligands has been related with the macrophage phenotype and strong evidence identifies the WNT signalling pathway as an emerging modulator of fibrosis. Methods The aim of...
Article
Background Vitamin D deficiency and a defective signalling has been reported in Crohn’s disease (CD) patients. Vitamin D signals through the vitamin D receptor (VDR) which is a member of the nuclear receptor family of transcription factors that play an immunoregulatory role in the gut. We have previously demonstrated that a single-nucleotide polymo...
Article
Background Fibrosis and fistula development constitute the main complications associated to Crohn’s disease. Notch signalling has been implicated in lung, kidney, liver, and cardiac fibrosis and in various disease conditions such as scleroderma. We aim to analyse here the pattern of NOTCH ligands, receptors, and effectors expression in surgical res...
Article
Background Intestinal fistula is a common complication in CD patients whose aetiology is unknown. It is associated with an exacerbated inflammation and epithelial-to-mesenquimal transition (EMT), a process which allows a switch from epithelial towards a fibrotic phenotype. Under inflammatory conditions, succinate is accumulated and activates its re...
Article
Full-text available
Succinate, an intermediate of the tricarboxylic acid cycle, is accumulated in inflamed areas and its signaling through succinate receptor (SUCNR1) regulates immune function. We analyze SUCNR1 expression in the intestine of Crohn's disease patients and its role in murine intestinal inflammation and fibrosis. We show that both serum and intestinal su...
Article
Full-text available
Background Vitamin D signaling modulates inflammation through the vitamin D receptor (VDR). The synonymous single nucleotide polymorphism (SNP) rs731236, located in the VDR gene, has been associated with a higher risk of Crohn’s disease (CD). We analyzed differences in VDR expression levels among CD patients who were homozygous for allelic variants...
Article
Full-text available
Background Intestinal fibrosis is a common complication associated with Crohn’s Disease (CD) which cannot be reverted with any drug and forces repeated surgery. It has been reported that succinate, a metabolite accumulated in inflammatory pathologies, plays an important role in the activation of synovial fibroblasts and hepatic stellate cells throu...
Article
Full-text available
Background Vitamin D signals through the vitamin D receptor (VDR) which is a member of the nuclear receptor family of transcription factors that play an immunoregulatory role in the gut. Defective signalling due to vitamin D deficiency or decreased mucosal VDR levels has been related to Crohn’s disease (CD). We aim to analyse the acute effects of V...
Article
Full-text available
Background and aims: Fibrosis is a common complication of Crohn's disease, and is related with dysregulated tissular repair following inflammation, in which macrophages play a central role. We have previously observed that STAT6-/- mice present delayed mucosal recovery after TNBS-induced colitis due to a deficiency in reparatory IL4/STAT6-dependen...
Article
Full-text available
Background: A defective autophagy is involved in the pathogenesis of inflammatory disorders such as IBD. Cross talk interactions between autophagy and inflammation have been reported and we analyse the effects of autophagy stimulators on murine colitis. Methods: Mice were treated with intrarectal administration of TNBS (3.5 mg/20 mg mice) and body...
Article
Full-text available
Background Vitamin D signaling modulates inflammation through the vitamin D receptor (VDR) which is a member of the nuclear receptor family of transcription factors. The presence of C instead of T in the single-nucleotide polymorphism (SNP) rs731236 in the VDR gene has been associated with a higher risk for Crohn's disease (CD). We analysed the rel...
Article
Full-text available
Background: STAT6 plays a crucial role in M2a macrophage polarization in vitro and these cells mediate mucosal healing in an acute model of TNBS-colitis through the expression of Wnt ligands [1]. We have recently reported that STAT6 deficiency favours fibrosis in a murine model of TNBS colitis [2] and we aim to characterize here the functional rele...
Article
Full-text available
Background: Intestinal fibrosis is a common complication of IBD. We have recently reported in STAT6 knockout mice treated with TNBS that intestinal fibrosis is associated with up-regulation of M2c macrophages which express high levels of Wnt10b. The aim of the present study is to analyze the direct effects of Wnt10b in fibrosis development in a mur...
Poster
Background:IntestinalfibrosisisacommoncomplicationofIBD.Fibrosisisaconsequenceoflocalchronicinflammationandischaracterizedbyanexcessiveextracellularmatrixdepositionandlossofnormalfunction.Residentmacrophagesplayakeyroleinmaintainingintestinalhomeostasisaswellasininjuryrepair,andtheirphenotypeevolvesduringthephasesofinflammation,remissionandwoundhea...
Poster
Intestinal fibrosis, which is caused by excessive extracellular matrix deposition, is a common complication of inflammatory bowel disease. Macrophages assume a wide spectrum of different functional phenotypes (M1, M2a, M2b, and M2c) that differ in the expression of surface proteins, transcription factors, and cytokine production. It is believed tha...

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