**1. Introduction**

Skeletal muscle tissue, making up approximately 40% of the total body mass in adult mam‐ mals, is composed of multinucleated contractile muscle cells, myofibers. Intramuscular connective tissue accounts for 1–10% of the skeletal muscle mass and varies substantially between muscles [1]. Muscle fibers are coated by an extracellular matrix material (ECM), called the basement membrane, and composed of two layers: an internal, basal lamina, directly linked to

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the plasma membrane of myofibers (sarcolemma), and an external, reticular lamina. Extracel‐ lular matrix surrounding muscle fibers is composed of collagens (dominated by collagen IV), laminins, fibronectin, and proteoglycans, formed by glycosaminoglycans bound to a protein core. Initially, it was considered as a structure that provides mechanical support for bearing force transmission [2]. The ECM gives mechanical structure to myofibers during contractions, provides the tissue with elasticproperties, andparticipates in the transmission offorce from the myofiber to tendon. It also serves as a basic mechanical support for nerves and vessels present in skeletal muscle tissue, and determines the spatial barrier between endothelium and muscle cell surface. A great progress in cell biology, molecular biology and genetics, gives new insight into skeletal muscle biology, and now it becomes evident that cells adhere to and connect with the ECM not only for structural stability but also for signaling. The integrins, heterodimeric transmembrane receptors comprising unrelated alpha and beta subunits, play critical roles in converting extracellular signals to intracellular responses (outside-in signaling) as well as in extracellular matrix interactions based upon intracellular changes (inside-out signaling) [3]. They bind to ECM or cell surface ligands and link the actin microfilament system with ECM, providing a connection between the ECM, the cytoskeleton, and signaling molecules. Integ‐ rins are considered as sensors of tensile strain at the cell surface, and together with the cytos‐ keleton form a mechanically sensitive organelle. Despite the large overall number of integrin receptor complexes, skeletal muscle integrin receptors are limited to seven alpha subunits, all associatedwiththebeta1integrinsubunit.Integrinsignaltransmissiondependsontheactivation of focal adhesion kinase (FAK), a nonreceptor tyrosine kinase, localized at focal adhesions. Integrin engagement causes the formation of transient signaling complex, initiated by the recruitment of Src-family protein SH2 to the FAK Tyr-397 autophosphorylation site, and by serving as a signaling element in cytoskeleton-associated networks [4]. Integrin-linked kinase (ILK), initially considered as a kinase, but, in fact, incapable to perform phosphorylation due to pseudoactive domain, mediates interactions of integrins with numerous cellular proteins and regulates focal adhesion assembly, cytoskeleton organization, and signaling [5]. The major enzymes responsible for the ECM breakdown under physiological conditions are matrix metalloproteinases (MMPs, or matrixins), which belong to a family of zinc-dependent and calcium-activated neutral endopeptidases, comprising secreted and membrane-associated members. MMPs are involved in degradation of the ECM and basement membrane; however, they also cleave a variety of other ECM-related proteins, including cytokines, chemokines, and growth factors [6]. There is some specificity of certain MMPs toward collagen types, that is, MMP-2 and 9 (gelatinases) primarily degrade type IV collagen and other compounds of the ECM in muscle, whereas MMP-1 and 8 (collagenases) traditionally are thought to break down types I and III collagen, being more relevant for tendon. MMP activities are regulated by tissue inhibitors of matrix metalloproteinases (TIMPs). Four TIMPs, responsible for the inhibition of over20MMPs,areidentified;ofthese,TIMP-1andTIMP-2arecapableofinhibiting,ofallMMPs, preferably MMP-2 and 9, respectively [1]. In addition to MMP-dependent mechanisms, TIMPs can alter cell growth and survival in an MMP-independent manner, mediated by integrins. A good example is TIMP-2, which regulates beta1 integrin expression and the size of myotubes formedduringmyoblastdifferentiation[7].MMPsplay animportantrole inskeletalmuscle cell growthanddifferentiation,astheyareengagedinreleaseandactivationofcytokinesandgrowth

factors. The main contributors to ECM assembly in skeletal muscle are resident fibroblasts; however, muscle cells also synthesize and secrete numerous ECM components and ECMrelated molecules, suggesting their active and direct participation in ECM remodeling. Thus, thecompositionoftheECMexertsmechanical,metabolic,hemodynamic,andangiogeniceffects in skeletal muscle tissue. The extracellular matrix and its receptors also provide an appropri‐ ate and permissive environment for muscle development and some ECM components, in addition to muscle-specific factors, can serve as good indicators of skeletal muscle function‐ ing. This chapter summarizes current knowledge on the role of ECM components related to skeletal muscle development and regeneration, which is of great importance for potential therapeutic interventions. It also focuses on the contribution of ECM in motor and metabolic functions of skeletal muscle tissue. Finally, the attention is paid on potential implications of changes in ECM assembly and function in health and disease.
