1,721,073 research outputs found
The Charming World of the Extracellular Matrix: A Dynamic and Protective Network of the Intestinal Wall
Full text linkThe intestinal extracellular matrix (ECM) represents a complex network of proteins that not only forms a support structure for resident cells but also interacts closely with them by modulating their phenotypes and functions. More than 300 molecules have been identified, each of them with unique biochemical properties and exclusive biological functions. ECM components not only provide a scaffold for the tissue but also afford tensile strength and limit overstretch of the organ. The ECM holds water, ensures suitable hydration of the tissue, and participates in a selective barrier to the external environment. ECM-to-cells interaction is crucial for morphogenesis and cell differentiation, proliferation, and apoptosis. The ECM is a dynamic and multifunctional structure. The ECM is constantly renewed and remodeled by coordinated action among ECM-producing cells, degrading enzymes, and their specific inhibitors. During this process, several growth factors are released in the ECM, and they, in turn, modulate the deposition of new ECM. In this review, we describe the main components and functions of intestinal ECM and we discuss their role in maintaining the structure and function of the intestinal barrier. Achieving complete knowledge of the ECM world is an important goal to understand the mechanisms leading to the onset and the progression of several intestinal diseases related to alterations in ECM remodeling
Rilevanza dell’apoptosi epiteliale nelle malattie gastrointestinali. Giornale di gastroenterologia 2003;8:1-21
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Liver metabolic zonation and hepatic microcirculation in carbon tetrachloride-induced experimental cirrhosis
No full textExtracellular Vesicles and Resistance to Anticancer Drugs: A Tumor Skeleton Key for Unhinging Chemotherapies
Full text linkAlthough surgical procedures and clinical care allow reaching high success in fighting most tumors, cancer is still a formidable foe. Recurrence and metastatization dampen the patients’ overall survival after the first diagnosis; nevertheless, the large knowledge of the molecular bases drives these aspects. Chemoresistance is tightly linked to these features and is mainly responsible for the failure of cancer eradication, leaving patients without a crucial medical strategy. Many pathways have been elucidated to trigger insensitiveness to drugs, generally associated with the promotion of tumor growth, aggressiveness, and metastatisation. The main mechanisms reported are the expression of transporter proteins, the induction or mutations of oncogenes and transcription factors, the alteration in genomic or mitochondrial DNA, the triggering of autophagy or epithelial-to-mesenchymal transition, the acquisition of a stem phenotype, and the activation of tumor microenvironment cells. Extracellular vesicles (EVs) can directly transfer or epigenetically induce to a target cell the molecular machinery responsible for the acquisition of resistance to drugs. In this review, we resume the main body of knowledge supporting the crucial role of EVs in the context of chemoresistance, with a particular emphasis on the mechanisms related to some of the main drugs used to fight cancer
Increased apoptosis and proliferation of colonic epithelial cells in dextran sulphate sodium-induced colitis in rats.
No full textFeatures of intestinal lesions in the clinical course of Inflammatory Bowel Diseases.
No full textInflammatory bowel diseases (IBD), including ulcerative colitis (UC) and Crohn’s disease (CD), are chronic, progressive and relapsing inflammatory disorders of unknown etiology. UC is characterized by inflammation of the large bowel mucosa and submucosa, whereas in CD inflammation is trans-mural and may involve various sites of the gastrointestinal tract. Superficial mucosal lesions are most prone to heal, whereas deep ulcers or transmural fissures may heal with more difficulty and may be followed by the development of fibrosis and strictures requiring surgery. Inflammation appears to be necessary to trigger the onset of the fibrotic process, but subsequently plays a minor role in its progression. In IBD, anti-inflammatory treatment does not prevent evolution of fibrosis once the process has started. Therefore, the mechanisms that regulate fibrosis appear to be distinct from those regulating inflammation. Intestinal fibrosis is due to an abnormal accumulation of extracellular matrix proteins producted by activated intestinal myofibroblasts. Increased evidence indicate that a number of molecules are involved in the development of the disease and a crosstalk between TGFβ/Smads pathway and αvβ6 integrin, mTOR and PPARγ could play a crucial role in the development of intestinal fibrosis. Animal models represent a useful tool to investigate the molecular and cellular mechanisms of intestinal inflammation and fibrosis and to test the effectiveness of novel therapeutic strategies for the prevention and treatment of intestinal fibrosis that still remain the major cause of surgical intervention
Can we prevent, reduce or reverse intestinal fibrosis in IBD?
No full textIntestinal fibrosis is a common complication of in inflammatory bowel disease
(IBD) and can occur in both ulcerative colitis (UC) and Crohn’s disease (CD), but is much more prevalent in CD. Fibrosis is a consequence of local chronic inflammation and is characterized by
abnormal deposition of extracellular matrix (ECM) proteins producted by activated myofibroblasts.
Current anti-inflammatory therapies used in IBD do not prevent nor they reverse established fibrosis and strictures. Despite the therapeutic advance in the treatment of IBD in the
last two decades, the incidence of intestinal strictures in CD has not significantly changed. This
implies that control of intestinal inflammation
does not necessarily affect the associated fibrotic
process. The conventional view that intestinal
fibrosis is an inevitable and irreversible process in patients with IBD is progressively changing in
light of improved understanding of the cellular
and molecular mechanisms that underline the pathogenesis of fibrosis. Comprehension of the
mechanisms of intestinal fibrosis may pave the way for the developments of anti-fibrotic agents
and of new possible therapeutic approches in
IBD. Nevertheless, there are important clinical issues
that need further investigations, in particular
the identification of factors relevant for the development
of the intestinal fibrosis in IBD and the need of accurate and effective monitoring of the fibrotic progression and of effectiveness of the
new proposed treatments
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