title: Cellular mechanisms of tissue fibrosis. 4. Structural and functional consequences of skeletal muscle fibrosis.
abstract: Skeletal muscle fibrosis can be a devastating clinical problem that arises from many causes, including primary skeletal muscle tissue diseases, as seen in the muscular dystrophies, or it can be secondary to events that include trauma to muscle or brain injury. The cellular source of activated fibroblasts (myofibroblasts) may include resident fibroblasts, adult muscle stem cells, or inflammatory or perivascular cells, depending on the model studied. Even though it is likely that there is no single source for all myofibroblasts, a common mechanism for the production of fibrosis is via the transforming growth factor-β/phosphorylated Smad3 pathway. This pathway and its downstream targets thus provide loci for antifibrotic therapies, as do methods for blocking the transdifferentiation of progenitors into activated fibroblasts. A structural model for the extracellular collagen network of skeletal muscle is needed so that measurements of collagen content, morphology, and gene expression can be related to mechanical properties. Approaches used to study fibrosis in tissues, such as lung, kidney, and liver, need to be applied to studies of skeletal muscle to identify ways to prevent or even cure the devastating maladies of skeletal muscle.
authors.affiliation: Department of Orthopaedic Surgery, University of California San Diego, San Diego, California 92093-0863, USA. rlieber@ucsd.edu
authors.forename: Richard L
authors.initials: RL
authors.lastname: Lieber
authors.forename: Samuel R
authors.initials: SR
authors.lastname: Ward
mesh_terms: D000818:Animals; D054338:Cell Transdifferentiation; D003094:Collagen / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005355:Fibrosis; D006801:Humans; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D009135:Muscular Diseases / Q000378:metabolism* / Q000473:pathology*; D058628:Myofibroblasts / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D055435:Myostatin / Q000378:metabolism; D051900:Smad3 Protein / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism; D060449:Wnt Signaling Pathway
chemical_list: C502426:CTHRC1 protein, human; D016326:Extracellular Matrix Proteins; C525911:MSTN protein, human; D055435:Myostatin; C497790:SMAD3 protein, human; D051900:Smad3 Protein; D016212:Transforming Growth Factor beta; D003094:Collagen
keywords: muscle mechanics; myofibroblast; passive mechanics; stiffness