Showing papers by "Rosario Donato published in 2012"
TL;DR: Extracellular S100 proteins exert regulatory activities on monocytes/macrophages/microglia, neutrophils, lymphocytes, mast cells, articular chondrocytes, endothelial and vascular smooth muscle cells, neurons, astrocytic cells, Schwann cells, epithelial cells, myoblasts and cardiomyocytes, thereby participating in innate and adaptive immune responses, cell migration and chemotaxis, tissue development and repair, and leukocyte and tumor
Abstract: The S100 protein family consists of 24 members functionally distributed into three main subgroups: those that only exert intracellular regulatory effects, those with intracellular and extracellular functions and those which mainly exert extracellular regulatory effects. S100 proteins are only expressed in vertebrates and show cell-specific expression patterns. In some instances, a particular S100 protein can be induced in pathological circumstances in a cell type that does not express it in normal physiological conditions. Within cells, S100 proteins are involved in aspects of regulation of proliferation, differentiation, apoptosis, Ca2+ homeostasis, energy metabolism, inflammation and migration/invasion through interactions with a variety of target proteins including enzymes, cytoskeletal subunits, receptors, transcription factors and nucleic acids. Some S100 proteins are secreted or released and regulate cell functions in an autocrine and paracrine manner via activation of surface receptors (e.g. the receptor for advanced glycation end-products and toll-like receptor 4), G-protein-coupled receptors, scavenger receptors, or heparan sulfate proteoglycans and N-glycans. Extracellular S100A4 and S100B also interact with epidermal growth factor and basic fibroblast growth factor, respectively, thereby enhancing the activity of the corresponding receptors. Thus, extracellular S100 proteins exert regulatory activities on monocytes/macrophages/microglia, neutrophils, lymphocytes, mast cells, articular chondrocytes, endothelial and vascular smooth muscle cells, neurons, astrocytes, Schwann cells, epithelial cells, myoblasts and cardiomyocytes, thereby participating in innate and adaptive immune responses, cell migration and chemotaxis, tissue development and repair, and leukocyte and tumor cell invasion.
1,042 citations
TL;DR: RAGE signaling physiologically repressed Pax7 transcription in SCs by upregulating myogenin, thereby accelerating muscle regeneration and limiting SC self-renewal, and was transiently expressed in activated, proliferating and differentiating satellite cells (SCs) in injured muscles.
Abstract: Expression of the paired-box 7 (PAX7) transcription factor is regulated during both myoblast proliferation and differentiation: high levels of PAX7 compromise myogenic differentiation because of excess and prolonged proliferation, whereas low levels of PAX7 result in precocious differentiation. We showed that myogenin repressed Pax7 transcription in differentiating myoblasts by binding to specific recognition sites in the Pax7 promoter, and that high-mobility group box 1 (HMGB1)-receptor for advanced glycation end-products (RAGE) signaling was required for myogenin induction and myogenin-dependent repression of Pax7 transcription. In addition, PAX7 negatively and myogenin positively regulated RAGE expression. RAGE, a multiligand receptor of the immunoglobulin superfamily, was not expressed in adult skeletal muscles, and was transiently expressed in activated, proliferating and differentiating satellite cells (SCs) in injured muscles. Compared with wild-type muscles, Rage(-/-) muscles exhibited increased numbers of basal SCs that were further increased in injured Rage(-/-) muscles following elevated myoblast asymmetric division; complete regeneration of injured Rage(-/-) muscles was found to be delayed by ~1 week. Thus, RAGE signaling physiologically repressed Pax7 transcription in SCs by upregulating myogenin, thereby accelerating muscle regeneration and limiting SC self-renewal.
77 citations
TL;DR: A review of studies of the physical and functional interactions of S100 proteins and ion channels reveals direct and indirect interactions with Ca2+, K+, Cl−, and ligand activated channels.
Abstract: S100 Ca2+-binding proteins have been associated with a multitude of intracellular Ca2+-mediated functions including regulation of the cell cycle, cell differentiation, cell motility and apoptosis, modulation of membrane-cytoskeletal interactions, transduction of intracellular Ca2+ signals, and in mediating learning and memory. S100 proteins are fine tuned to read the intracellular free Ca2+ concentration, modulate protein phosphorylation, and compete with calmodulin for binding sites, which makes them strong candidates to modulate neuronal electrical behaviour. Certain S100s are secreted from cells and are found in extracellular fluids where they exert unique extracellular functions. In addition to their neurotrophic activity, certain S100 proteins modulate neuronal electrical discharge activity and appear to act on ion channels. The first reports regarding these effects suggested S100-mediated alterations in Ca2+ fluxes, K+ currents and neuronal discharge activity. Recent reports revealed direct and indirect interactions with Ca2+, K+, Cl- and ligand activated channels. This review focuses on studies of the physical and functional interactions of S100 proteins and ion channels.
76 citations
TL;DR: It is proposed that S100B is a danger signal released from injured muscles that participates in skeletal muscle regeneration by activating the promyogenic RAGE or the mitogenic bFGF/FGFR1 depending on its own concentration, the absence or presence of bF GF, and myoblast density.
Abstract: In high-density myoblast cultures S100B enhances basic fibroblast growth factor (bFGF) receptor 1 (FGFR1) signaling via binding to bFGF and blocks its canonical receptor, receptor for advanced glycation end-products (RAGE), thereby stimulating proliferation and inhibiting differentiation. Here we show that upon skeletal muscle injury S100B is released from myofibers with maximum release at day 1 post-injury in coincidence with satellite cell activation and the beginning of the myoblast proliferation phase, and declining release thereafter in coincidence with reduced myoblast proliferation and enhanced differentiation. By contrast, levels of released bFGF are remarkably low at day 1 post-injury, peak around day 5 and decline thereafter. We also show that in low-density myoblast cultures S100B binds RAGE, but not bFGF/FGFR1 thereby simultaneously stimulating proliferation via ERK1/2 and activating the myogenic program via p38 MAPK. Clearance of S100B after a 24-h treatment of low-density myoblasts results in enhanced myotube formation compared with controls as a result of increased cell numbers and activated myogenic program, whereas chronic treatment with S100B results in stimulation of proliferation and inhibition of differentiation due to a switch of the initial low-density culture to a high-density culture. However, at relatively high doses, S100B stimulates the mitogenic bFGF/FGFR1 signaling in low-density myoblasts, provided bFGF is present. We propose that S100B is a danger signal released from injured muscles that participates in skeletal muscle regeneration by activating the promyogenic RAGE or the mitogenic bFGF/FGFR1 depending on its own concentration, the absence or presence of bFGF, and myoblast density.
46 citations
TL;DR: Preliminary results suggest that the transplant product creates a suitable microenvironment for muscle regeneration and growth potentially applicable to DMD patients.
Abstract: Duchenne muscular dystrophy (DMD), a progressive muscle degenerative disease associated with chronic inflammation, necrosis and fibrosis, is currently treated with antiinflammatory steroids, despite their limited efficacy and undesired side effects. Testicular Sertoli cells (SCs) have been successfully implanted to treat many experimental diseases due to their ability to secrete trophic, antiinflammatory and immunomodulatory molecules (Mital et al., 2010). We transplanted microencapsulated SCs, within highly biocompatible microcapsules (Luca et al., 2007) into the peritoneal cavity of mdx mice, an animal model of DMD. Three weeks after transplantation, skeletal muscles from SC-treated mice, compared with muscles from mock-treated mice, showed: i) dramatically reduced number of infiltrated cells, including (MAC3+) macrophages; ii) a marked decrease in necrotic myofibers, and an increased number of regenerated (normally sized and centrally nucleated) myofibers; and, iii) a significant decrease in fibrous tissue infiltration. Moreover, SC-treated, but not mock-treated mdx mice showed recovery of muscle performance in treadmill endurance tests and a comparable resistance to exercise-induced muscle damage to that of untreated wildtype mice. These preliminary results suggest that our transplant product creates a suitable microenvironment for muscle regeneration and growth potentially applicable to DMD patients.