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Your search keyword '"Pompili, Simona"' showing total 4 results
Start Over Author "Pompili, Simona" Topic inflammatory bowel disease
4 results on '"Pompili, Simona"'

1. DDS-induced colorectal fibrosis in mice: anti-fibrotic effects of GED 0507-34 levo, a novel PPARγ ligand

Author

Pompili, Simona, Sferra, Roberta, Vetuschi, Antonella, Latella, Giovanni, Gaudio, Eugenio, Cicchinelli, Sara, and Speca, Silvia

Subjects
Inflammatory Bowel Disease, animal model, fibrosis, TGFβ/Smads, PPARγ, digestive system diseases
Abstract

Intestinal fibrosis is a progressive process characterized by de novo synthesis and uncontrolled deposition of extracellular matrix components (ECM) following a tissue chronic inflammation mainly regulated by Transforming Growth Factor (TGF)β/ Smads pathway. Frequently associated to Inflammatory Bowel Disease (IBD), intestinal fibrosis may lead to stenosis and obstructions that require surgery up to 75% of patients as drugs currently used in IBD are unable to improve fibrostenosis lesions (1). Peroxisome proliferator-activated receptor (PPAR)-γ is able to antagonize (TGF) β/Smads and could be an crucial target to develop novel antifibrotic therapeutic strategies (2). Aim of this study is to evaluate the antifibrotic action of a novel PPARγ agonist, GED 0507-34 levo, in colonic fibrosis in mice. Immunohistochemistry and immunoblotting evaluations, TGFβ1, CTGF, Collagen types I-III, Smad3, α-SMA, were performed in in three groups of C57BL/6 mice: Dextran Sulphate Sodium (DSS) colitis group, DSS+GED group and controls. Evident macroscopic and microscopic lesions in the most of colons of DSS treated mice were observed compared to DSS+GED mice and controls. The tissue levels of the main markers of fibrosis resulted significantly increased in DSS mice and restored by administration of GED. GED seems to prevents ECM colonic deposition and to improve the intestinal fibrotic lesions by its ability in controlling TGFβ/Smads pathway signalling activation., Italian Journal of Anatomy and Embryology, Vol 119, No 1 (Supplement) 2014

Published
2015
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2. Epithelial-to-Mesenchymal Transition (EMT) in experimental intestinal fibrosis

Author

Vetuschi, Antonella, Pompili, Simona, Flati, Vincenzo, De Berardinis, Luca, Di Gregorio, Jacopo, Latella, Giovanni, and Sferra, Roberta

Subjects
Intestinal Fibrosis, EMT, E-cadherin, β-catenin, GSK3-beta, inflammatory bowel disease, intestinal fibrosis, EMT, intestinal fibrosis, inflammatory bowel disease
Abstract

Inflammatory Bowel Diseases (IBD) are chronic and progressive inflammatory disorders that may result in intestinal fibrosis, characterized by excessive and uncon- trolled deposition of extracellular matrix components (ECM). Other than Smad- dependent the profibrotic effects of TGFβ signaling that leads to a phenotype switch of intestinal mesenchymal cells, resulting in proliferation and collagene deposition (1), source of fibrotic tissue comes from the process called Epithelial-to-Mesenchymal Transition (EMT), in which also epithelial cells acquire fibroblastic phenotype and related function (2). The purpose of our study was to evaluate the expression of pro- tein markers of EMT in a mouse model of intestinal fibrosis and their changes after the administration of the experimental drug GED- 0507-34 Levo, that is able to inhibit and revert the fibrotic phenotypic switch. Immunohistochemistry (IHC) and immunofluorescence (IF) evalutations for E-cadherin and β-catenin were performed in three groups of C57BL/6 mice: Dextran Sulphate Sodium (DSS) colitis group, DSS+GED group and controls. In the same groups E-cadherin, β-catenin, p-GSK3-beta and GSK3-beta were evaluated by immunoblotting. In IHC and IF analysis, was observed a significant decrease of E-cadherin and β-catenin expression in DSS group compared to control. GED administration was able to revert the DSS effect by increasing the expression of both proteins to levels similar to the control. Comparable results were obtained by immunoblotting. Furthermore the immunoblotting assay showed that the known EMT inhibitor GSK3-beta is activated in the DSS+GED group suggesting that GSK3-beta activity is required for the restoration of the epithelial phenotype exerted by GED. Taken together, our results indicates that the EMT is another cause of colla- gen deposition in our mouse model and thus it could be a valid target for the devel- opment of a treatment for intestinal fibrosis., Italian Journal of Anatomy and Embryology, Vol. 120, No. 1 (Supplement) 2015

Published
2015

3. Role of glycogen synthase kinase-3β and PPAR-γ on epithelial-to-mesenchymal transition in DSS-induced colorectal fibrosis.

Author

Di Gregorio, Jacopo, Sferra, Roberta, Speca, Silvia, Vetuschi, Antonella, Dubuquoy, Caroline, Desreumaux, Pierre, Pompili, Simona, Cristiano, Loredana, Gaudio, Eugenio, Flati, Vincenzo, and Latella, Giovanni

Subjects
GLYCOGEN synthases, PEROXISOME proliferator-activated receptors, CELL transformation, EXTRACELLULAR matrix, MESENCHYMAL stem cells, MYOFIBROBLASTS
Abstract

Background: Intestinal fibrosis is characterized by abnormal production and deposition of extracellular matrix (ECM) proteins by activated myofibroblasts. The main progenitor cells of activated myofibroblasts are the fibroblasts and the epithelial cells, the latter through the epithelial-mesenchymal transition (EMT). Aim: To evaluate the action of the new PPAR-γ modulator, GED-0507-34 Levo (GED) on the expression of EMT associated and regulatory proteins such as TGF-β, Smad3, E-cadherin, Snail, ZEB1, β-catenin, and GSK-3β, in a mouse model of DSS-induced intestinal fibrosis. Methods: Chronic colitis and fibrosis were induced by oral administration of 2.5% DSS (w/v) for 6 weeks. GW9662 (GW), a selective PPAR-γ inhibitor, was also administered by intraperitoneal injection at the dose of 1 mg/kg/day combined with GED treatment. All drugs were administered at the beginning of the second cycle of DSS (day 12). 65 mice were randomly divided into five groups (H2O as controls n = 10, H2O+GED n = 10, DSS n = 15, DSS+GED n = 15, DSS+GED+GW n = 15). The colon was excised for macroscopic examination and histological and morphometric analyses. The level of expression of molecules involved in EMT and fibrosis, like TGF-β, Smad3, E-cadherin, Snail, ZEB1, β-catenin, GSK-3β and PPAR-γ, was assessed by immunohistochemistry, immunofluorescence, western blot and Real Time PCR. Results: GED improved the DSS-induced chronic colitis and fibrosis. GED was able to reduce the expression of the main fibrosis markers (α-SMA, collagen I-III and fibronectin) as well as the pivotal pro-fibrotic molecules IL-13, TGF-β and Smad3, while it increased the anti-fibrotic PPAR-γ. All these GED effects were nullified by co-administration of GW with GED. Furthermore, GED was able to normalize the expression levels of E-cadherin and β-catenin and upregulated GSK-3β, that are all known to be involved both in EMT and fibrosis. Conclusions: The DSS-induced intestinal fibrosis was improved by the new PPAR-γ modulator GED-0507-34 Levo through the modulation of EMT mediators and pro-fibrotic molecules and through GSK-3β induction. [ABSTRACT FROM AUTHOR]

Published
2017
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4. Can Nrf2 Modulate the Development of Intestinal Fibrosis and Cancer in Inflammatory Bowel Disease?

Author

Pompili, Simona, Sferra, Roberta, Gaudio, Eugenio, Viscido, Angelo, Frieri, Giuseppe, Vetuschi, Antonella, and Latella, Giovanni

Subjects
*INFLAMMATORY bowel diseases, *FIBROSIS, *CANCER, *MORPHOGENESIS, *NEURODEGENERATION
Abstract

One of the main mechanisms carried out by the cells to counteract several forms of stress is the activation of the nuclear factor erythroid 2-related factor (Nrf2) signaling. Nrf2 signaling controls the expression of many genes through the binding of a specific cis-acting element known as the antioxidant response element (ARE). Activation of Nrf2/ARE signaling can mitigate several pathologic mechanisms associated with an autoimmune response, digestive and metabolic disorders, as well as respiratory, cardiovascular, and neurodegenerative diseases. Indeed, several studies have demonstrated that Nrf2 pathway plays a key role in inflammation and in cancer development in many organs, including the intestine. Nrf2 appears to be involved in inflammatory bowel disease (IBD), an immune-mediated chronic and disabling disease, with a high risk of developing intestinal fibrotic strictures and cancer. Currently, drugs able to increase cytoprotective Nrf2 function are in clinical trials or already being used in clinical practice to reduce the progression of some degenerative conditions. The role of Nrf2 in cancer development and progression is controversial, and drugs able to inhibit abnormal levels of Nrf2 are also under investigation. The goal of this review is to analyze and discuss Nrf2-dependent signals in the initiation and progression of intestinal fibrosis and cancers occurring in IBD. [ABSTRACT FROM AUTHOR]

Published
2019
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