title: Integrins, muscle agrin and sarcoglycans during muscular inactivity conditions: an immunohistochemical study.
abstract: Sarcoglycans are transmembrane proteins that seem to be functionally and pathologically as important as dystrophin. Sarcoglycans cluster together to form a complex, which is localized in the cell membrane of skeletal, cardiac, and smooth muscle. It has been proposed that the dystrophin-glycoprotein complex (DGC) links the actin cytoskeleton with the extracellular matrix and the proper maintenance of this connection is thought to be crucial to the mechanical stability of the sarcolemma. The integrins are a family of heterodimeric cell surface receptors which play a crucial role in cell adhesion including cell-matrix and intracellular interactions and therefore are involved in various biological phenomena, including cell migration, and differentiation tissue repair. Sarcoglycans and integrins play a mechanical and signaling role stabilizing the systems during cycles of contraction and relaxation. Several studies suggested the possibility that integrins might play a role in muscle agrin signalling. On these basis, we performed an immunohistochemical analyzing sarcoglycans, integrins and agrin, on human skeletal muscle affected by sensitive-motor polyneuropathy, in order to better define the correlation between these proteins and neurogenic atrophy due to peripheral neuropathy. Our results showed the existence of a cascade mechanism which provoke a loss of regulatory effects of muscle activity on costameres, due to loss of muscle and neural agrin. This cascade mechanism could determine a quantitative modification of transmembrane receptors and loss of alpha7B could be replaced and reinforced by enhanced expression of the alpha7A integrin to restore muscle fiber viability. Second, it is possible that the reduced cycles of contraction and relaxation of muscle fibers, during muscular atrophy, provoke a loss of mechanical stresses transmitted over cell surface receptors that physically couple the cytoskeleton to extracellular matrix. Consequently, these mechanical changes could determine modifications of chemical signals through variations of pathway structural integrins, and alpha7A could replace alpha7B.
authors.affiliation: Department of Biomorphology and Biotechnologies, Policlinico Universitario G. Martino, University of Messina, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Anastasi
authors.forename: G
authors.initials: G
authors.lastname: Cutroneo
authors.forename: G
authors.initials: G
authors.lastname: Santoro
authors.forename: A
authors.initials: A
authors.lastname: Arco
authors.forename: G
authors.initials: G
authors.lastname: Rizzo
authors.forename: C
authors.initials: C
authors.lastname: Trommino
authors.forename: P
authors.initials: P
authors.lastname: Bramanti
authors.forename: L
authors.initials: L
authors.lastname: Soscia
authors.forename: A
authors.initials: A
authors.lastname: Favaloro
mesh_terms: D018171:Agrin / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D001706:Biopsy; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D007124:Immunoenzyme Techniques; D016023:Integrins / Q000378:metabolism*; D018613:Microscopy, Confocal; D009043:Motor Activity / Q000502:physiology; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000648:ultrastructure; D011115:Polyneuropathies / Q000378:metabolism* / Q000473:pathology; D049031:Sarcoglycans / Q000378:metabolism*
chemical_list: D018171:Agrin; D015415:Biomarkers; D016023:Integrins; D049031:Sarcoglycans