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      Implications of Skeletal Muscle Extracellular Matrix Remodeling in Metabolic Disorders: Diabetes Perspective

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          Abstract

          The extracellular matrix (ECM) provides a scaffold for cells, controlling biological processes and providing structural as well as mechanical support to surrounding cells. Disruption of ECM homeostasis results in several pathological conditions. Skeletal muscle ECM is a complex network comprising collagens, proteoglycans, glycoproteins, and elastin. Recent therapeutic approaches targeting ECM remodeling have been extensively deliberated. Various ECM components are typically found to be augmented in the skeletal muscle of obese and/or diabetic humans. Skeletal muscle ECM remodeling is thought to be a feature of the pathogenic milieu allied with metabolic dysregulation, obesity, and eventual diabetes. This narrative review explores the current understanding of key components of skeletal muscle ECM and their specific roles in the regulation of metabolic diseases. Additionally, we discuss muscle-specific integrins and their role in the regulation of insulin sensitivity. A better understanding of the importance of skeletal muscle ECM remodeling, integrin signaling, and other factors that regulate insulin activity may help in the development of novel therapeutics for managing diabetes and other metabolic disorders.

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          Most cited references64

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          CD44: from adhesion molecules to signalling regulators.

          Cell-adhesion molecules, once believed to function primarily in tethering cells to extracellular ligands, are now recognized as having broader functions in cellular signalling cascades. The CD44 transmembrane glycoprotein family adds new aspects to these roles by participating in signal-transduction processes--not only by establishing specific transmembrane complexes, but also by organizing signalling cascades through association with the actin cytoskeleton. CD44 and its associated partner proteins monitor changes in the extracellular matrix that influence cell growth, survival and differentiation.
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            Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs): Positive and negative regulators in tumor cell adhesion.

            Cells adhere to one another and/or to matrices that surround them. Regulation of cell-cell (intercellular) and cell-matrix adhesion is tightly controlled in normal cells, however, defects in cell adhesion are common in the majority of human cancers. Multilateral communication among tumor cells with the extracellular matrix (ECM) and neighbor cells is accomplished through adhesion molecules, ECM components, proteolytic enzymes and their endogenous inhibitors. There is sufficient evidence to suggest that reduced adherence is a tumor cell property engaged during tumor progression. Tumor cells acquire the ability to change shape, detach and easily move through spaces disorganizing the normal tissue architecture. This property is due to changes in expression levels of adhesion molecules and/or due to elevated levels of secreted proteolytic enzymes, including matrix metalloproteinases (MMPs). Among other roles, MMPs degrade the ECM and, therefore, prepare the path for tumor cells to migrate, invade and spread to distant secondary areas, where they form metastasis. Tissue inhibitors of metalloproteinases or TIMPs control MMP activities and, therefore, minimize matrix degradation. Both MMPs and TIMPs are involved in tissue remodeling and decisively regulate tumor cell progression including tumor angiogenesis. In this review, we describe and discuss data that support the important role of MMPs and TIMPs in cancer cell adhesion and tumor progression. Published by Elsevier Ltd.
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              Is Open Access

              Role of Myokines in Regulating Skeletal Muscle Mass and Function

              Loss of skeletal muscle mass and strength has recently become a hot research topic with the extension of life span and an increasingly sedentary lifestyle in modern society. Maintenance of skeletal muscle mass is considered an essential determinant of muscle strength and function. Myokines are cytokines synthesized and released by myocytes during muscular contractions. They are implicated in autocrine regulation of metabolism in the muscle as well as in the paracrine/endocrine regulation of other tissues and organs including adipose tissue, the liver, and the brain through their receptors. Till date, secretome analysis of human myocyte culture medium has revealed over 600 myokines. In this review article, we summarize our current knowledge of major identified and characterized myokines focusing on their biological activity and function, particularly in muscle mass and function.

                Author and article information

                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                28 May 2020
                June 2020
                : 21
                : 11
                : 3845
                Affiliations
                [1 ]Department of Medical Biotechnology, Yeungnam University, Gyeongsan 38541, Korea; ahmadkhursheed2008@ 123456gmail.com (K.A.); inhochoi@ 123456ynu.ac.kr (I.C.)
                [2 ]Department of Biomedical Science, Daegu Catholic University, Gyeongsan 38430, Korea
                Author notes
                [* ]Correspondence: ylee325@ 123456cu.ac.kr
                Author information
                https://orcid.org/0000-0002-1095-8445
                Article
                ijms-21-03845
                10.3390/ijms21113845
                7312063
                32481704
                e948f2ea-fc99-42c2-9e16-d660e1e62f45
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 02 May 2020
                : 25 May 2020
                Categories
                Review

                Molecular biology
                extracellular matrix,remodeling,insulin resistance,integrin,diabetes
                Molecular biology
                extracellular matrix, remodeling, insulin resistance, integrin, diabetes

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