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Microgravity Effects on the Matrisome cells Review Microgravity Effects on the Matrisome Ludmila Buravkova * , Irina Larina, Elena Andreeva and Anatoly Grigoriev Institute of Biomedical Problems, Russian Academy of Sciences, Khoroshevskoye Shosse 76a, 123007 Moscow, Russia; [email protected] (I.L.); [email protected] (E.A.); [email protected] (A.G.) * Correspondence: [email protected]; Tel.: +7-499-195-22-43 Abstract: Gravity is fundamental factor determining all processes of development and vital activity on Earth. During evolution, a complex mechanism of response to gravity alterations was formed in multicellular organisms. It includes the “gravisensors” in extracellular and intracellular spaces. Inside the cells, the cytoskeleton molecules are the principal gravity-sensitive structures, and outside the cells these are extracellular matrix (ECM) components. The cooperation between the intracellular and extracellular compartments is implemented through specialized protein structures, integrins. The gravity-sensitive complex is a kind of molecular hub that coordinates the functions of various tissues and organs in the gravitational environment. The functioning of this system is of particular importance under extremal conditions, such as spaceflight microgravity. This review covers the current understanding of ECM and associated molecules as the matrisome, the features of the above components in connective tissues, and the role of the latter in the cell and tissue responses to the gravity alterations. Special attention is paid to contemporary methodological approaches to the matrisome composition analysis under real space flights and ground-based simulation of its effects on Earth. Keywords: space flights; microgravity; matrisome; connective tissues; stromal lineage cells; tran- Citation: Buravkova, L.; Larina, I.; scriptomics; proteomics Andreeva, E.; Grigoriev, A. Microgravity Effects on the Matrisome. Cells 2021, 10, 2226. https://doi.org/10.3390/ 1. Introduction cells10092226 In recent decades, significant progress has been made in the understanding of basic principles of the cellular response to the alterations of gravitational stimulus due to the Academic Editor: Agapios Sachinidis development of cellular and molecular biology approaches [1–4]. According to the current mechanochemical hypothesis, integrins and other cell surface Received: 22 July 2021 receptors play an important role in the physical interaction between extracellular matrix Accepted: 24 August 2021 (ECM) and cytoskeleton. Mechanically forced deformations in these linked structures Published: 27 August 2021 switch on/off various intracellular molecular events involving the cytoskeleton structures and associated signal transduction cascades [4–7]. Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in ECM, as a counterpart of the gravisensivity network, remains much less studied than published maps and institutional affil- the cell surface structures, cytoskeleton and related intracellular events. At the same time, iations. it is well known that the skeleton with abundant ECM as well as muscle tissues are most sensitive to space flight microgravity [2,8–11]. It is obvious that progress in the study of the response to microgravity and the development of approaches to the prevention of the negative effects of gravity deprivation is impossible without considering the role of ECM. Copyright: © 2021 by the authors. 2. Current Concept of the Extracellular Matrix as a Complex of Structural and Licensee MDPI, Basel, Switzerland. Regulatory Molecules: Matrisome This article is an open access article ECM is a complex three-dimensional macromolecular network that provides support distributed under the terms and for tissues and organs in multicellular organisms. According to the classical statements, all conditions of the Creative Commons Attribution (CC BY) license (https:// ECM components are composed of fibrillar (insoluble) and amorphous (soluble) ones [12]. creativecommons.org/licenses/by/ Structured fibrillar part consists of collagens, elastins, fibronectins, and laminins, forming 4.0/). ECM fibers and fibrills. Amorphous (soluble) components primarily are represented Cells 2021, 10, 2226. https://doi.org/10.3390/cells10092226 https://www.mdpi.com/journal/cells Cells 2021, 10, 2226 2 of 18 Cells 2021, 10, 2226 2 of 18 forming ECM fibers and fibrills. Amorphous (soluble) components primarily are repre- bysented glycoproteins by glycoproteins and proteoglycans. and proteoglycans. Besides, Besides, the ECM the ECM may may be also be also distinguished distinguished as pericellularas pericellular and and interstitial interstitial compartments compartments differing differing in in their their structure/composition structure/composition [[13].13]. TheThe repertoirerepertoire ofof ECMECM componentscomponents isis tissuetissue specific.specific. The ECM functions functions are are far far beyond beyond the the physical physical support support of the of theintegrity integrity and andelasticity elas- ticityof tissues. of tissues. It is a Itdynamic is a dynamic structure structure that is thatcontinuously is continuously being reconstructed being reconstructed to control to controlhomeostasis, homeostasis, regulating regulating various various cellular cellular processes processes such as such proliferation, as proliferation, migration, migration, differ- differentiation,entiation, viability, viability, and morphogenesis and morphogenesis [14–16]. [14 Currently,–16]. Currently, ECM is ECMconsidered is considered as a multi- as acomponent multicomponent structure, structure, including including a complex a complexof structural of structuralmolecules, molecules, remodeling remodeling molecules, molecules,and ECM-associated and ECM-associated biologically biologically active metabolites. active metabolites. InIn 1984,1984, MartinMartin et et al. al. used used the the term term “matrisome” “matrisome” to to describe describe the the structural structural organization organiza- oftion the of componentsthe components of basementof basement membranes, membranes, defining defining it it as as “supramolecular “supramolecular complexcomplex formingforming thethe functionalfunctional ECMECM units”units” [[17].17]. NabaNaba andand colleaguescolleagues havehave suggestedsuggested toto expandexpand thethe conceptconcept ofof matrisomematrisome consideringconsidering the latterlatter as an ensembleensemble ofof ECMECM structuralstructural (core)(core) elementselements andand ECM-associatedECM-associated proteins.proteins. AccordingAccording toto thethe authors,authors, thethe latterlatter includeinclude linkedlinked solublesoluble moleculesmolecules (growth(growth factors,factors, cytokines,cytokines, etc.),etc.), regulatoryregulatory moleculesmolecules (proteases(proteases andand theirtheir inhibitors),inhibitors), and and ECM-affiliated ECM-affiliated proteins proteins (Figure (Figure1)[ 1)18 ,[18,19].19]. Since Since many many ECM ECM molecules mole- arecules insoluble are insoluble and difficult and difficult to isolate, to isolate, various various proteomic proteomic methods methods are a useful are a tool useful to predict tool to thepredict relevance the relevance and structure and structure of proteins of protei to certainns to certain matrisome matrisome compartments, compartments, based based on theon the specific specific domains domains of matrisome of matrisome molecules. molecules. The The above above has significantlyhas significantly expanded expanded the numberthe number of ECM-associated of ECM-associated components components [18]. [18]. Figure 1. Matrisome and microgravity. According to the current concept an ensemble of ECM struc- turalFigure (core) 1. Matrisome elements andand ECM-associatedmicrogravity. According proteins representsto the current a complex concept structure an ensemble called of matrisome. ECM Thestructural activity (core) of matrisome elements elementsand ECM-associated is governed proteins by different represents mechanical a complex forces, structure strongly called affected by microgravitymatrisome. The (µg). activity of matrisome elements is governed by different mechanical forces, strongly affected by microgravity (µg). The data on most principal ECM and ECM-associated components as well as their involvementThe data in on the most physiological principal processes ECM and have ECM- beenassociated revised in components detail [14,20 as–29 well]. Below as their we willinvolvement shortly summarize in the physiological the available processes information have focusing been revised on matrisome-related in detail [14,20–29]. molecules. Below we willMain shortly ECM summarize structural the components available belonginginformation to focusing collagens’ on superfamilymatrisome-related should mol- be mentionedecules. first of all among the core matrisome molecules. This superfamily includes 28 moleculesMain ECMcomposed structural of 46 components various polypeptide belongingα-chains to collagens’ forming superfamily triple helices. should Fibrillar be collagensmentioned are first abundant of all among in the the organs core matrisome resistant to molecules. stretching This (skin, superfamily bones, ligaments, includes and 28 cartilage). In addition to the primary structural function, collagen networks transmit Cells 2021, 10, 2226 3 of 18 intercellular signals, which affect various cellular functions, including migration, adhesion, angiogenesis, and tissue development and repair [23]. Several proteoglycans, glycoproteins, and enzymes are involved in the formation
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