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Evaluation of antiinflammatory and antifibrotic effects of phenolic extracts (olive cream enriched with active Lactobacilli strains) in a Dextran Sulphate Sodium (DSS) experimental colitis in rats.
Italy (SISM) - Università degli Studi del L'Aquila, L'Aquila
Biotechnologies and Informatics
Department of Biotechnological and Applied Clinical Sciences
Prof. Antonella Vetuschi and Prof. Roberta Sferra
Required: English Accepted: Italian
Type of Research Project
- Basic science
What is the background of the project?
Inflammatory Bowel Diseases (IBD) are characterized by the development of intestinal fibrosis that may lead to stenosis and obstructions and require surgery up to 75% of patients as drugs currently used are unable to improve fibrostenosis lesions. Intestinal fibrosis is a progressive process characterized by uncontrolled deposition of extracellular matrix components (ECM) due to the activation of intestinal mesenchymal cells. Of the several molecules regulating these activities, Transforming Growth Factor (TGF)β/Smads pathway appear to play a pivotal role. Existing therapies, predominantly aminosalicylates, steroids and immunomodulators, can relieve the inflammatory symptoms but they do not significantly improve the stricture lesions of the bowel. As the concept of intestinal fibrosis in IBD has changed from being a static and irreversible entity to a dynamic and reversible disease, as also occur in other organs, novel therapeutic strategies are under investigation to target specific molecules in the process of fibrogenesis with the aim to prevent, reduce or even reverse intestinal fibrosis in IBD.
What is the aim of the project?
Aim of the project is to evaluate the potential anti-inflammatory and antifibrotic action of olive cream containing active Lactobacilli strains in an experimental intestinal fibrosis and its/their ability to interfere with the main pathway involved in the disease.
What techniques and methods are used?
Fragments of many organs, previously excised, will undergo to structural evaluations as follow: In vivo histomorphological and immunohistochemical analyses -Formalin buffered fixation -Paraffin embedding - Hematoxylin and Eosin/ Masson's Trichrome stainings Immunohistochemical analyses for different antibodies: IL-13, TGFβ, Collagen I-III, Smad3, pSmad3, Smad7, α-SMA, CTGF, PDGF, mTOR, pmTOR, PPAR-γ, S1P, P13-K, AKT, AGE, RAGE. -Observations under optical microscope -Quantitative analyses of immunopositive areas In vitro analyses Western Blot analyses for: IL-13, TGFβ, Collagen I-III, Smad3, pSmad3, Smad7, α-SMA, CTGF, PDGF, mTOR, pmTOR, PPAR-γ, S1P, P13-K, AKT, AGE, RAGE.
What is the role of the student?
- The student will observe the practical experiments but will be highly involved in the analysis of the results
- The tasks will be done under supervision
What are the tasks expected to be accomplished by the student?
Paraffin embedding, microtomy and paraffin section preparations, histomorphological and immunohistochemical stainings, observation under optical microscope end images analyses
Will there be any theoretical teaching provided (preliminary readings, lectures, courses, seminars etc)
Preliminary explanation about the content of the project and the methods that will be used.
What is expected from the student at the end of the research exchange? What will be the general outcome of the student?
- The student will prepare a scientific report
What skills are required of the student? Is there any special knowledge or a certain level of studies needed?
Basic knowledge of Histology
Are there any legal limitations in the student’s involvement
Type of students accepted
This project accepts: - Medical students - Pre-Medical students from the American-British system - Students in biomedical fields
- 1) Dextran sulfate sodium (DSS) colitis in rats: clinical; structural; and ultrastructural aspects. Gaudio E; Taddei G; Vetuschi A; Sferra R; Frieri G; Ricciardi G; Caprilli R. Dig Dis Sci. 1999 Jul;44(7):1458-75.
- 2) Features of intestinal lesions in the clinical course of inflammatory bowel diseases.Vetuschi A; Latella G; Pompili S; Gaudio E; Sferra R. Ital J Anat Embryol. 2014;119(3):286-303.
- 3) Role of glycogen synthase kinase-3β and PPAR-γ on epithelial-to-mesenchymal transition in DSS-induced colorectal fibrosis. Di Gregorio J; Sferra R; Speca S; Vetuschi A; Dubuquoy C; Desreumaux P; Pompili S; Cristiano L; Gaudio E; Flati V; Latella G. PLoS One. 2017 Feb 16;12(2):e0171093. doi: 10.1371/journal.pone.0171093.
- 4) Interaction between Sphingosine kinase/Sphingosine 1 phosphate and Transforming Growth Factor-β/Smads pathways in experimental intestinal fibrosis: an in vivo immunohistochemical study. Sferra R; Pompili S; Ventura L; Dubuquoy C; Speca S; Gaudio E; Latella G; Vetuschi A. Eur J Histochem 31; 62(3)2018. Doi 10.4081/ejh2018.2956.
- 5) PPAR-γ with its anti-inflammatory and antifibrotic action could be an effective therapeutic target in IBD. Vetuschi A; Pompili S; Gaudio E; Latella G; Sferra R. Eur Rev Med Pharmacol Sci; accepted for publication; 2018.
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