Skeletal Muscle Extracellular Matrix – What Do We Know About Its Composition, Regulation, and Physiological Roles? A Narrative Review

Abstract

Skeletal muscle represents the largest body-composition component in humans. In addition to its primary function in the maintenance of upright posture and the production of movement, it also plays important roles in many other physiological processes, including thermogenesis, metabolism and the secretion of peptides for communication with other tissues. Research attempting to unveil these processes has traditionally focused on muscle fibers, i.e., the contractile muscle cells. However, it is a frequently overlooked fact that muscle fibers reside in a three-dimensional scaffolding that consists of various collagens, glycoproteins, proteoglycans, and elastin, and is commonly referred to as extracellular matrix (ECM). While initially believed to be relatively inert, current research reveals the involvement of ECM cells in numerous important physiological processes. In interaction with other cells, such as fibroblasts or cells of the immune system, the ECM regulates muscle development, growth and repair and is essential for effective muscle contraction and force transmission. Since muscle ECM is highly malleable, its texture and, consequently, physiological roles may be affected by physical training and disuse, aging or various diseases, such as diabetes. With the aim to stimulate increased efforts to study this still poorly understood tissue, this narrative review summarizes the current body of knowledge on (i) the composition and structure of the ECM, (ii) molecular pathways involved in ECM remodeling, (iii) the physiological roles of muscle ECM, (iv) dysregulations of ECM with aging and disease as well as (v) the adaptations of muscle ECM to training and disuse.

Smart ECM-Based Electrospun Biomaterials for Skeletal Muscle Regeneration

“…Skeletal muscle is an important body-composition component in humans and plays a key role in voluntary movement and locomotion [ 85 ]. In addition, skeletal muscle is involved in other physiological processes, including thermogenesis, metabolism, and the secretion of numerous peptides for communication with other tissues [ 85 ]. For these reasons, the maintenance of skeletal muscle health is of vital importance.…”

“…The IMCT is typically organized in three layers: (i) the endomysium, representing the innermost layer that encloses individual muscle fibers; (ii) the perimysium bundling groups of muscle fibers; (iii) the epimysium enveloping the entire muscle. The IMCT contains various forms of collagens with types I and III being the most abundant [ 85 ]. The endomysium interfaces with the myofiber sarcolemma at a specialized basement membrane, which consists primarily of type IV collagen and laminin.…”

“…The endomysium interfaces with the myofiber sarcolemma at a specialized basement membrane, which consists primarily of type IV collagen and laminin. Collagen type IV, a helical molecule, produces a network structure that with laminin, constitutes the basis of the basal lamina, directly linked to the sarcolemma of myofibers [ 85 ].…”

Remodeling the Skeletal Muscle Extracellular Matrix in Older Age—Effects of Acute Exercise Stimuli on Gene Expression

“…Nonetheless, a less described but important structure that may change with advancing age is the muscle’s extracellular matrix (ECM). The ECM consists of a mesh of collagenous components as well as a mixture of further macromolecules, including various glycoproteins, proteoglycans and elastin [ 13 ]. Its functions in mature muscle are manifold and include not only the mechanical support of the muscle fibers, nerves and blood vessels but also the communication with other cells such as myoblasts [ 14 ], fibroblasts [ 15 ] or inflammatory cells [ 16 ].…”

Role of the Extracellular Matrix in Loss of Muscle Force With Age and Unloading Using Magnetic Resonance Imaging, Biochemical Analysis, and Computational Models

“…Such ECM remodeling may lead to altered permeability and, ultimately, promote disuse atrophy. It is important to note that aging and disuse may induce changes in the structure and biochemical composition of the ECM, which are expected to be associated with impaired transmission of contractile force through lateral pathways [i.e., through shearing between adjacent muscle fibers across costameres and the network of intramuscular connective tissue (IMCT)] (Csapo et al, 2020).…”