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      The Charming World of the Extracellular Matrix: A Dynamic and Protective Network of the Intestinal Wall

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          Abstract

          The 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.

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          Most cited references239

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          Extracellular vesicles: Exosomes, microvesicles, and friends

          Cells release into the extracellular environment diverse types of membrane vesicles of endosomal and plasma membrane origin called exosomes and microvesicles, respectively. These extracellular vesicles (EVs) represent an important mode of intercellular communication by serving as vehicles for transfer between cells of membrane and cytosolic proteins, lipids, and RNA. Deficiencies in our knowledge of the molecular mechanisms for EV formation and lack of methods to interfere with the packaging of cargo or with vesicle release, however, still hamper identification of their physiological relevance in vivo. In this review, we focus on the characterization of EVs and on currently proposed mechanisms for their formation, targeting, and function.
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            Remodelling the extracellular matrix in development and disease.

            The extracellular matrix (ECM) is a highly dynamic structure that is present in all tissues and continuously undergoes controlled remodelling. This process involves quantitative and qualitative changes in the ECM, mediated by specific enzymes that are responsible for ECM degradation, such as metalloproteinases. The ECM interacts with cells to regulate diverse functions, including proliferation, migration and differentiation. ECM remodelling is crucial for regulating the morphogenesis of the intestine and lungs, as well as of the mammary and submandibular glands. Dysregulation of ECM composition, structure, stiffness and abundance contributes to several pathological conditions, such as fibrosis and invasive cancer. A better understanding of how the ECM regulates organ structure and function and of how ECM remodelling affects disease progression will contribute to the development of new therapeutics.
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              Communication by Extracellular Vesicles: Where We Are and Where We Need to Go.

              In multicellular organisms, distant cells can exchange information by sending out signals composed of single molecules or, as increasingly exemplified in the literature, via complex packets stuffed with a selection of proteins, lipids, and nucleic acids, called extracellular vesicles (EVs; also known as exosomes and microvesicles, among other names). This Review covers some of the most striking functions described for EV secretion but also presents the limitations on our knowledge of their physiological roles. While there are initial indications that EV-mediated pathways operate in vivo, the actual nature of the EVs involved in these effects still needs to be clarified. Here, we focus on the context of tumor cells and their microenvironment, but similar results and challenges apply to all patho/physiological systems in which EV-mediated communication is proposed to take place.
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                Author and article information

                Contributors
                Journal
                Front Med (Lausanne)
                Front Med (Lausanne)
                Front. Med.
                Frontiers in Medicine
                Frontiers Media S.A.
                2296-858X
                16 April 2021
                2021
                : 8
                : 610189
                Affiliations
                [1] 1Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila , L'Aquila, Italy
                [2] 2Department of Life, Health and Environmental Sciences, Gastroenterology Unit, University of L'Aquila , L'Aquila, Italy
                [3] 3Department of Anatomical, Histological, Forensic Medicine, and Orthopedic Sciences, Sapienza University of Rome , Rome, Italy
                Author notes

                Edited by: Pedro M. Baptista, Health Research Institute of Aragon (IIS Aragon), Spain

                Reviewed by: Xiaofei Sun, University of California, San Francisco, United States; Alfredo Cappariello, Bambino Gesù Ospedale Pediatrico, Italy

                *Correspondence: Roberta Sferra roberta.sferra@ 123456univaq.it

                This article was submitted to Gastroenterology, a section of the journal Frontiers in Medicine

                †These authors have contributed equally to this work

                Article
                10.3389/fmed.2021.610189
                8085262
                33937276
                ee31d07f-921a-4393-a28d-51ae147a7d4d
                Copyright © 2021 Pompili, Latella, Gaudio, Sferra and Vetuschi.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 25 September 2020
                : 22 March 2021
                Page count
                Figures: 3, Tables: 6, Equations: 0, References: 240, Pages: 19, Words: 15128
                Categories
                Medicine
                Review

                bowel,intestinal wall,extracellular matrix,basement membrane,interstitial matrix,mmps,timps

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