University of Perugia
MyoLab
Cellular and Molecular Myology
Prof. Guglielmo Sorci
Dept. Medicine and Surgery
University of Perugia
&
Interuniversity Institute of Myology (IIM)
Our Research Aims
- Investigating the biology of muscle precursor cells, muscle regeneration, muscle atrophy (including sarcopenia and cancer cachexia), muscular dystrophy, and rhabdomyosarcoma, with particular regards to RAGE (receptor for advanced glycation end-products) and the calcium-binding protein S100B.
- Investigating the engraftment of microencapsulated Sertoli cells as a treatment to Duchenne muscular dystrophy.
- Investigating the alterations induced by microgravity in human satellite cells and muscles.
- Investigating the efficacy of herbal extracts in counteracting muscle atrophy.
Lab Members
Dr. Laura Salvadori
Post-Doc
laurasalvadori1988@
gmail.com
Research
MAIN PROJECTS
Fighting WESTERN diet-derived AGEs (advanced glycation end products) with natural compounds to mitigate muscle wasting in sarcobesity (WESTERNAGE)
Granted by the European Union (NextGenerationEU) and Ministero dell'Università e della Ricerca
PRIN2022 PNRR (Prot. P2022Z4EB5)
Skeletal muscle has a pivotal role in the maintenance of whole-body metabolism, and the loss of muscle mass and functionality (muscle wasting; MW) predisposes to several diseases. MW is a common feature of noncommunicable chronic diseases (NCDs), such as obesity, diabetes, and sarcopenia, contributing to their deleterious outcomes. Sarcobesity, i.e., MW coincident with increased fat tissue, is a growing, urgent and poorly understood complex syndrome with detrimental consequences and elevated healthcare costs. The nutritional transition to a "Western diet" (WD) increases the development of insulin resistance and metabolic inflexibility predisposing to MW and sarcobesity by sustaining systemic/local inflammation and oxidative stress. WD foods contain high advanced glycation end-products (AGEs), a group of glycosylated adducts also endogenously formed. AGE accumulation over time alters the function of tissue cross-linked proteins and sustains oxidative stress and inflammation via the receptor RAGE. Indeed, AGEs/RAGE interactions have been implicated in multiple metabolic disorders, including obesity, insulin resistance, and diabetes. In diabetic and geriatric patients, accumulation of AGEs in skeletal muscle, blood, and skin, has been associated with sarcopenia, and RAGE signaling induces MW in several conditions. The mechanisms underlying WD-dependent MW, including the potential role of dietary AGEs (dAGEs)/RAGE axis have not been investigated so far. We hypothesize that high dAGEs might be mediators of WD-dependent MW and contribute to the onset and progression of sarcobesity, predisposing to earlier and more severe metabolic consequences, including type 2 diabetes (T2D). By using in vitro and in vivo preclinical models, and an observational study in patients with obesity and T2D, our project aims to: i) discover and dissect the role of dAGEs/RAGE axis in WD-induced MW; ii) unravel genes, pathways and metabolomic signature affected by WD, thus identifying therapeutic targets for sarcobesity; iii) test anti-dAGEs
natural compounds as an approach to maintain muscle mass and functionality, and reduce the risk of comorbidities associated to WD intake; iv) correlate the level of dietary and endogenous AGEs with the severity of sarcopenia; v) identify dAGEs as potential reliable biomarkers of MW risk in patients with obesity and T2D, with high clinical relevance in prevention and early screening of sarcobesity.The synergy between basic science and clinical research will allow the validation in patients of the main findings obtained in preclinical models conferring to the project high translational potential and future socio-economic impact. The already ongoing collaboration between the research units and the consistent collection of preliminary results ensure the project feasibility that will accelerate the identification of strategies to mitigate the detrimental effects of WD and related NCDs in line with the PNRR objectives and WHO agenda goals.
Definition of a validated food supplement from controlled cultivation of Mediterranean plants as a natural polypill to counteract osteosarcopenia in elderly (PhytoMuscleBone)
Granted by the European Union (NextGenerationEU) and Ministero dell'Università e della Ricerca
PRIN2022 (Prot. 2022B8KE33)
The concomitant loss of muscle mass (sarcopenia) and bone deterioration (osteoporosis) predispose elderly subjects to frailty, bone fractures and loss of independence, compromising life quality and leading to increased morbidity and mortality. Considering the increasing life expectancy in the Western countries, osteosarcopenia represents an urgent and still unresolved health problem against which no pharmacological drugs are available. Although physical exercise, together with an adequate diet, has shown positive results in osteosarcopenia, the reduced motor skills typical of elderly people limit the clinical use of exercise-based approaches. In recent years, the scientific interest in the use of medicinal plants to counteract the mechanisms underlining several pathological conditions has increased, and some herbal extracts have shown positive effects in maintaining muscle or bone homeostasis. The project aims to study and create a dietary supplement able to counteract the loss of muscle and bone mass associated with aging starting from plants typical of the Mediterranean area and cultivated under controlled conditions in order to enrich these species in metabolites active in conferring the best anti-osteosarcopenic power. Several Mediterranean plants will be selected for their content in functional and bioactive compounds, and herbal extracts will be obtained and progressively evaluated in the following in vitro models: i) C2C12 myotubes treated with different atrophying stimuli and human myotubes derived from sarcopenic subjects, as models of muscle atrophy; ii) RANKL-treated RAW 264.7 cells and human osteoclasts, as models of osteoclast differentiation, responsible for bone resorption; and iii) BMP2-treated C2C12 cells and human osteoblasts, as models of osteoblast differentiation and bone mineralization. The resulting most efficacious plants will be cultivated under different cultivation protocols (combining irrigation, inorganic fertilization inputs and balsamic times) and the relative herbal extracts will be re-evaluated in parallel on human sarcopenic myotubes, osteoclasts or osteoblasts. The best three herbal extracts in terms of anti-sarcopenic and anti-osteoporotic effects will be analysed for active metabolite content, and the mechanisms of action investigated. The three herbal extracts will be mixed together to obtain an herbal formulation and the analysis of the anti-osteosarcopenic power of the exosomes released by muscle and bone cells following treatment with the selected herbal formulation will be performed in vitro. Finally, the herbal formulation will be evaluated in terms of specific pathological scores, histological assessment and gene expression profiling in geriatric mice developing osteosarcopenia to assess its efficacy in vivo. Thus, we will define cultivation protocols to obtain a validated food supplement from Mediterranean plants useful as a natural polypill in counteracting osteosarcopenia in elderly subjects.
Accelerating the use of microencapsulated Sertoli cells to treat DMD patients
Granted by Duchenne Parent Project NL
Sertoli cells (SeC) of the testes are endowed with trophic and anti-inflammatory properties and have been extensively used to protect co-grafted tissues or to take benefit from their released factors in many experimental models of diseases. A single intraperitoneal injection of biocompatible alginate-based microencapsulated porcine SeC (MC-SeC) into dystrophic mice translated into recovery of muscle morphology and performance in the absence of pharmacological immunosuppression. Injected MC-SeC behave as a drug-delivery system secreting a cocktail of factors that cross the peritoneum and reach all body muscles through the blood flow, thus restraining muscle inflammation and upregulating utrophin expression. Moreover, SeC exert promyogenic, antifibrotic and anti-atrophic effects on myoblasts/myotubes, and induce utrophin expression in human DMD myotubes irrespective of the mutation in a heregulin β1/ErbB2/ERK1/2-dependent manner. Thus, the SeC-based approach appears as a potential universal treatment to DMD. Based on the evaluation of the TREAT NMD Advisory Committee for Therapeutics (TACT), the project is aimed to evaluate in mdx mice: i) subcutaneous vs intraperitoneal engraftment of MC-SeC; ii) the effects of MC-SeC on the heart and tissues other than muscles; iii) the effects of MC-SeC on muscle physiology and performance; iv) the factors mainly involved in the beneficial effects of MC-SeC and their mechanism of action; v) the use of MC-SeC in combination with steroids. This investigation will improve the translational potential of SeC-based treatments to DMD and Becker muscular dystrophy (BMD) patients, endowed with several advantages over the therapeutic approaches currently under evaluation and substantially devoid of side effects.
Preclinical targeting of RAGE (receptor for advanced glycation end-products)
to counteract cancer cachexia
Granted by AIRC (Associazione Italiana per la Ricerca sul Cancro); Project #24762 (2021-2026)
Cachexia, a multifactorial syndrome affecting more than half patients with advanced cancer and responsible for ~20% of cancer-associated deaths, is still poorly understood and no standard cures are available. Muscle atrophy due to systemic inflammation and tumor-released factors is a major clinical feature of cachexia leading to weight loss, and worsening quality of life and patients’ response to anti-cancer therapy. The identification of valuable biomarkers of early cachexia is of great importance to treat patients in the reversible phase of the syndrome. RAGE (receptor for advanced glycation end-products) signaling concurs to muscle development and homeostasis, however in cancer conditions RAGE sustains hallmarks of cancer cachexia due to hyperstimulation by high serum levels of its ligands, S100B and HMGB1, which also induce muscle wasting per se. Genetic ablation of RAGE in tumor-bearing mice translates into reduced serum levels of cachexia-inducing factors, delayed loss of muscle mass and strength, reduced tumor progression, and increased survival. Thus, molecular targeting of RAGE might represent a therapeutic strategy to counteract the cachectic syndrome. Our project is aimed to: i) dissect the mechanism(s) used by RAGE to sustain cachexia in tumor, immune and muscle components; ii) investigate the effects of FPS-ZM1 (RAGE inhibitor) or pentamidine (S100B inhibitor) in comparison with glucocorticoids or ghrelin treatment or physical exercise, in adult, aged and under-chemotherapy tumor-bearing mice; iii) establish a correlation between preclinical models of cachexia and cachectic patients with respect to muscle RAGE and serum levels of RAGE ligands. We expect: i) to identify the mechanism(s) through which RAGE sustains cachexia and in which component(s) (muscular or non-muscular); ii) that inactivation of RAGE using FPS-ZM1 and/or pentamidine reduces systemic inflammation and favours the maintenance of muscle mass and functionality in cancer conditions, even under chemotherapy treatment or during aging; and iii) to find a positive correlation between the severity of cachexia, RAGE expression in muscles and the serum levels of RAGE ligands in preclinical models and in cancer patients. Pharmacological inhibition of RAGE activity might represent a promising approach to counteract muscle wasting in cancer conditions, and might be used as an exercise-mimetics in cachectic patients with elevated muscle weakness.
RAGE, sRAGE and/or RAGE ligands might represent potential biomarkers to monitor the cachectic stage and the efficacy of anti-cachectic treatments, which is of great importance as reliable biomarkers of cachexia are still lacking.
Use of microencapsulated Sertoli cells in Duchenne muscular dystrophy. Towards an application to human patients
Granted by Parent Project Onlus, Italy
Duchenne muscular dystrophy (DMD) is an X-linked disease due to lack of dystrophin, leading to progressive muscle degeneration, impaired locomotion and premature death. Persistent muscle degeneration is associated with a condition of chronic inflammation causing muscle necrosis and fibrosis. Sertoli cells (SeC) have the ability to produce immunomodulatory and trophic factors. SeC have been long used to create an ectopic immune-privileged environment to prolong survival of co-transplanted cells. Encapsulation has represented an improvement for the use of SeC. We reported that a single intraperitoneal injection of microencapsulated SeC (SeC-MC) is beneficial to dystrophic mdx mice. Injected SeC-MC behave as a drug-delivery system secreting factors that reach muscle tissue through the circulation, where reduce the inflammation and induce the expression of the dystrophin paralogue, utrophin, leading to rescue of muscle morphology and performance.
Although this novel therapeutic approach to DMD has translational potential (SeC are isolated from specific pathogens-free pigs, encapsulated in clinical grade alginate, injected with non-invasive procedure, and without any immunosuppression), further aspects need to be investigated that is the aim of this project: i) SeC-MC dose-response; ii) effects of SeC on canine and human dystrophic myoblasts in vitro; iii) morphology of SeC inside the microcapsules over time; iv) the role of SeC in inflammation using utrophin-deficient mdx (mdx/Utrn-/-) mice; and v) the safety of SeC treatment by the use of experimental models of infection and cancer. The results will give us important information about SeC biology necessary in view of their possible application to DMD patients.
MyoGravity
Multidisciplinary approach to the analysis of the functional alterations induced by microgravity in human satellite cells, and study of possible countermeasures
Granted by ASI (Italian Space Agency)
Long-time exposure to microgravity induces alteration of homeostasis in organs and tissues including skeletal muscles, which undergo atrophy with loss of mass and strength due to loss of muscle fibers and alteration of their composition. Particularly for long time flights such condition is of paramount relevance. Investigating the molecular mechanisms of muscle atrophy induced by microgravity is essential for establishing clinical approach/intervention. Satellite cells (SC) are responsible for growth, maintenance and repair of the muscle tissue. The adult SC of muscle tissue that reside between the basal lamina and the sarcolemma have the ability to activate, proliferate and form new muscle fibers or repair damaged ones. The activity of SC is under the control of intracellular and extracellular factors that are spatially and temporally organized. Microgravity conditions may be able to induce muscle atrophy by influencing the biology and the functionality of the SC. The research objectives are: 1) to study the changes induced by microgravity in the biology of human SC; 2) to compare the effects induced in human SC during the simulated microgravity on Ground with those induced by the real microgravity onboard the International Space Station (ISS); 3) to evaluate the effects in murine muscle cells of muscle-specific overexpression of IGF-1 as countermeasure to microgravity-induced muscle atrophy. The results of this project can be useful to understand any alterations at the level of property of SC of human skeletal muscle induced by exposure to microgravity, both simulated and real. The knowledge of the changes in the properties of SC, combined with changes in the ability of SC to respond to certain extracellular factors, will allow to design future interventions (nutritional and/or pharmacological) to fight the muscle wasting process induced by microgravity and encourage growth and maintenance of muscle mass during long-term space travel.
(The project is coordinated by Prof. Stefania Fulle, University of Chieti-Pescara, Italy, and involves the University Sapienza of Rome and the University of L'Aquila)
Inhibition of RAGE as a therapeutic approach to Duchenne muscular dystrophy
Granted by Duchenne Parent Project NL
Duchenne muscular dystrophy (DMD) is an X-linked pathology characterized by progressive muscle degeneration and chronic inflammation that causes muscle necrosis and fibrosis. Indeed, DMD patients are treated with antiinflammatory steroids, despite their limited efficacy and undesired side effects. RAGE, a multiligand receptor involved in inflammation and myogenesis, is not expressed in adult muscle tissue, but it is highly expressed in immune cells, regenerating myofibers during muscle regeneration, and dystrophic muscle tissue. To establish the effective role of RAGE in DMD muscles we generated a dystrophic (mdx) mouse lacking RAGE (mdx/Ager-/- mouse), which shows significantly reduced necrotic myofibers and immune cell infiltrate suggesting that targeting RAGE might result beneficial to DMD muscles. The aims of the project are to characterize the mdx/Ager-/- mouse, and to test the effects of RAGE inhibition by the specific inhibitor, FPS-ZM1, in DMD animals as a therapeutic approach. We will analyze muscles of mdx/Ager-/- mice at different ages, with particular focus on inflammatory cells. In mdx mice, we will analyze the effects in vitro and in vivo (i.p. injections) of different doses and durations of FPS-ZM1 treatment in comparison with glucocorticoids treatment to find an optimal condition for recovery of muscle morphology and performance. We will perform histological, immunohistochemical, western blot, FACS and PCR analyses of markers of inflammation, muscle differentiation, fibrosis, necrosis and autophagy, and functional evaluation. We expect that inhibition of RAGE in DMD animals by FPS-ZM1 results in reduced muscle inflammation, necrosis and fibrosis, and favors muscle functionality.
Evaluation of the efficacy of herbal preparations to counter induced muscular atrophy and sarcopenia. Formulation of a suitable herbal product.
Granted by Regione Umbria (A.R.CO. Fellowship)
In collaboration with Laboratori Biokyma Srl (Anghiari, Italy) (www.biokyma.com), leader in the production of officinal plants, and the research groups of Prof. Ferruccio Poli, University of Bologna (Bologna, Italy) and Prof. Stefania Fulle, University of Chieti-Pescara (Chieti, Italy). The project is aimed at developing herbal formulations useful in counteracting muscle atrophy associated with inflammatory diseases, use of steroid drugs or physiologically associated with aging.
Published Work
Salvadori L., Chiappalupi S., Arato I., Mancuso F., Calvitti M., Marchetti M.C., Riuzzi F., Calafiore R., Luca G., Sorci G. (2021) Sertoli Cells Improve Myogenic Differentiation, Reduce Fibrogenic Markers, and Induce Utrophin Expression in Human DMD Myoblasts. Biomolecules 11(10):1504; https://doi.org/10.3390/biom11101504
Chiappalupi S., Salvadori L., Donato R., Riuzzi F., Sorci G. (2021) Hyperactivated RAGE in comorbidities as a risk factor for severe COVID-19. The role of RAGE-RAS crosstalk. Biomolecules 11:876; https://10.3390/biom11060876
Chiappalupi S., Salvadori L., Vukasinovic A., Donato R., Sorci G.1, Riuzzi F.1 (2021) Targeting RAGE to prevent SARS-CoV-2-mediated multiple organ failure: Hypotheses and perspectives. Life Sci. 272:119251; doi: 10.1016/j.lfs.2021.119251; 1 Shared senior authorship
Salvadori L., Mandrone, M., Manenti, T., Ercolani, C., Cornioli, L., Lianza, M., Tomasi, P., Chiappalupi, S., Di Filippo, E.S., Fulle, S., Poli F., 1, Riuzzi F.1 (2021) Identification of Withania somnifera-Silybum marianum-Trigonella foenum-graecum formulation as a nutritional supplement to contrast muscle atrophy and sarcopenia. Nutrients 13:49; dx.doi.org/10.3390/nu13010049; 1 Shared senior authorship
Chiappalupi S.1, Sorci G.1, Vukasinovic A., Salvadori L., Sagheddu R., Coletti D., Renga G., Romani L., Donato R.2 and Riuzzi F.2 (2020) Targeting RAGE prevents muscle wasting and prolongs survival in cancer cachexia. J. Cachexia Sarcopenia Muscle 11(4):929-946; doi: 10.1002/jcsm.12561. 1 Contributed equally; 2 Shared senior authorship
Riuzzi F., Chiappalupi S., Arcuri C., Giambanco I., Sorci G.1 and Donato R.1 (2020) S100 proteins in obesity: liaisons dangereuses. Cell. Mol. Life Sci. 77:129-47. doi: 10.1007/s00018-019-03257-4; 1Shared senior authorship
Chiappalupi S., Salvadori L., Luca G., Riuzzi F., Calafiore R., Donato R. and Sorci G. (2019) Do porcine Sertoli cells represent an opportunity for Duchenne muscular dystrophy? Cell Proliferation 26:e12599. doi: 10.1111/cpr.12599
Riuzzi F.1, Sorci G.1, Arcuri C., Giambanco I., Bellezza I., Minelli A. and Donato R. (2018) Cellular and molecular mechanisms of sarcopenia: the S100B perspective. J. Cachexia Sarcopenia Muscle. Accepted for publication; 1Contributed equally
Riuzzi F.1, Sorci G.1, Sagheddu R., Chiappalupi S., Salvadori L. and Donato R. (2018) RAGE in the pathophysiology of skeletal muscle. J Cachexia Sarcopenia and Muscle. doi: 10.1002/jcsm.12350; 1Contributed equally
Sagheddu R., Chiappalupi S., Salvadori L., Riuzzi F., Donato R. and Sorci G. (2018) Targeting RAGE as a potential therapeutic approach to Duchenne muscular dystrophy. Hum. Mol. Genet. Doi: 10.1093/hmg/ddy288
Luca G., Arato I., Sorci G., Cameron D., Hansen B., Baroni T., Donato R., White D. and Calafiore R. (2018) Sertoli cells for cell transplantation: preclinical studies and future perspectives. Andrology 6(3): 385-95; dx.doi.org/10.1111/andr.12484
Donato R., Sorci G. and Giambanco I. (2018) S100A6. Encyclopedia of Signaling Molecules, 2nd Edition, Springer, pp. 4805-4813
Chiappalupi S., Salvadori L., Luca G., Riuzzi F., Calafiore R., Donato R. and Sorci G. (2017) Employment of microencapsulated Sertoli cells as a new tool to treat Duchenne muscular dystrophy. J. Funct. Morphol. Kinesiol. 2(4):47
Riuzzi F., Beccafico S., Sagheddu R., Chiappalupi S., Giambanco I., Bereshchenko O., Riccardi C., Sorci G.1 and Donato R.1 (2017) Levels of S100B protein drive the reparative process in acute muscle injury and muscular dystrophy. Sci. Rep. 7(1):1253; doi: 10.1038/s41598-017-12880-9; 1Shared Senior authorship
Donato R., Sorci G. and Giambanco I. (2017) S100A6 protein: functional roles. Cell. Mol. Life Sci. 74(15):2749-60; doi: 10.1007/s00018-017-2526-9
Donato R., Sorci G. and Giambanco I. (2017) Le proteine S100. Ligand Assay 22(1):11-44. Cover figure assigned
Chiappalupi S., Luca G., Mancuso F., Madaro L., Fallarino F., Nicoletti C., Calvitti M., Arato I., Falabella F., Salvadori L., Di Meo A., Bufalari A., Giovagnoli S., Calafiore R., Donato R. and Sorci G. (2016) Intraperitoneal injection of microencapsulated Sertoli cells restores muscle morphology and performance in dystrophic mice. Biomaterials 75:313-26; dx.doi.org/10.1016/j.biomaterials.2015.10.029
Chiappalupi S., Luca G., Mancuso F., Madaro L., Fallarino F., Nicoletti C., Calvitti M., Arato I., Falabella F., Salvadori L., Di Meo A., Bufalari A., Giovagnoli S., Calafiore R., Donato R. and Sorci G. (2015) Effects of intraperitoneal injection of microencapsulated Sertoli cells on chronic and presymptomatic dystrophic mice. Data in Brief 5:1015-21; dx.doi.org/10.1016/j.dib.2015.11.016
Matino D., Gargaro M., Santagostino E., Di Minno M.N.D., Castaman G., Morfini M., Rocino A., Mancuso M.E., Di Minno G., Coppola A., Talesa V.N., Volpi C., Vacca C., Orabona C., Iannitti R., Mazzucconi M.G., Santoro C., Tosti A., Chiappalupi S., Sorci G., Tagariello G., Belvini D., Radossi P., Landolfi R., Fuchs D., Boon L., Pirro M., Marchesini E., Grohmann U., Puccetti P., Iorio A., and Fallarino F. (2015) IDO1 suppresses inhibitor development in hemophilia A treated with factor VIII. J. Clin. Invest. 125(10):3766-81; doi:10.1172/JCI81859
Beccafico S., Morozzi G., Marchetti M.C., Riccardi C., Sidoni A., Donato R. and Sorci G. (2015) Artesunate induces ROS-mediated apoptosis and counteracts tumor growth in vivo in embryonal rhabdomyosarcoma cells. Carcinogenesis 36(9):1071-83; doi:10.1093/carcin/bgv098
Alaggio R., Midrio P., Sgrò A., Piovan G., Guzzardo V., Donato R., Sorci G., Lago P., Gamba P.G. (2015) Congenital diaphragmatic hernia: focus on abnormal muscle formation. J. Pediatr. Surg. 50(3):388-93; doi:10.1016/j.jpedsurg.2014.08.005
Chiappalupi S., Riuzzi F., Fulle S., Donato R., Sorci G. (2014) Defective RAGE activity in embryonal rhabdomyosarcoma cells results in high PAX7 levels that sustain migration and invasiveness. Carcinogenesis 35:2382-92; doi: 10.1093/carcin/bgu176
Riuzzi F.1, Sorci G.1, Sagheddu R.1, Sidoni A., Alaggio R., Ninfo V., Donato R. (2014) RAGE signaling deficiency in rhabdomyosarcoma cells causes upregulation of PAX7 and uncontrolled proliferation. J. Cell Sci. 127:1699-711; doi:10.1242/jcs.136259; 1Contributed equally
Faggi F., Mitola S., Sorci G., Riuzzi F., Donato R., Codenotti S., Poliani P.L., Cominelli M., Vescovi R., Rossi S., Calza S., Colombi M., Penna F., Costelli P., Perini I., Sampaolesi M., Monti E., Fanzani A. (2014) Phosphocaveolin-1 enforces tumor growth and chemoresistance in rhabdomyosarcoma. PLoS ONE 9(1):e84618; doi:10.1371/journal.pone.0084618
Iannitti R.G., Casagrande A., De Luca A., Cunha C., Sorci G., Riuzzi F., Borghi M., Galosi C., Massi-Benedetti C., Oury T.D., Cariani L., Russo M., Porcaro L., Colombo C., Majo F., Lucidi V., Fiscarelli E., Ricciotti G., Lass-Flörl C., Ratclif L., Esposito A., De Benedictis F.M., Donato R., Carvalho A., Romani L. (2013) Hypoxia promotes danger-mediated inflammation via RAGE in Cystic Fibrosis. Am. J. Resp. Crit. Care Med. 188(11):1338-50; doi:10.1164/rccm.201305-0986OC
Dormoy-Raclet V., Cammas A., Celona B., Lian X. J., van der Giessen K.1, Zivojnovic M., Brunelli S., Riuzzi F., Sorci G., Wilhelm B., Di Marco S., Donato R., Bianchi M. E. and Gallouzi I.-E. (2013) HuR and miR-1192 regulate myogenesis by modulating the translation of HMGB1 mRNA. Nat. Commun. 4:2388; doi:10.1038/ncomms3388
Fanzani A., Monti E., Donato R. and Sorci G. (2013) Muscular dystrophies share pathogenetic mechanisms with muscle sarcomas. Trends Mol. Med. 19(9):546-54, doi: 10.1016/j.molmed.2013.07.001
Sorci G., Riuzzi F., Arcuri C., Tubaro C., Bianchi R., Giambanco I. and Donato R. (2013) S100B protein in tissue development, repair and regeneration. World J. Biol. Chem. 4(1): 1-12; All the authors contributed equally
Donato R., Riuzzi F. and Sorci G. (2013) Causes of elevated serum levels of S100B protein in athletes. Eur. J. Appl. Physiol. 113:819-20
Sorci G., Riuzzi F., Giambanco I. and Donato R. (2013) RAGE in tissue homeostasis, repair and regeneration. Biochim. Biophys. Acta – Mol. Cell Res. 1833:101-9
Donato R., Cannon B.R., Sorci G., Riuzzi F., Hsu K., Weber D.J. and Geczy C.L. (2013) Functions of S100 proteins. Curr. Mol. Med. 13:24-57
Riuzzi F.1, Sorci G.1, Sagheddu R. and Donato R. (2012) HMGB1/RAGE regulates muscle satellite cell homeostasis via p38 MAPK/myogenin-dependent repression of Pax7 transcription. J. Cell Sci. 125(6):1440-54. Cover figure assigned; 1Contributed equally
Riuzzi F.1, Sorci G.1, Beccafico S. and Donato R. (2012) S100B engages RAGE or bFGF/FGFR1 in myoblasts depending on its own concentration and myoblast density. Implications for muscle regeneration. PLoS ONE 7(1): e28700, doi:10.1371/journal.pone.0028700; 1Contributed equally
Cunha C., Giovannini G., Pierini A., Bell A.S., Sorci G., Riuzzi F., Donato R., Rodrigues F., Velardi A., Aversa F., Romani L., Carvalho A. (2011) Genetically-determined hyperfunction of the S100B/RAGE axis is a risk factor for aspergillosis in stem cell transplant recipients. PLoS ONE 6(11): e27962, doi: 10.1371/journal.pone.0027962
Riuzzi F.1, Sorci G.1 and Donato R. (2011) S100B protein regulates myoblast proliferation and differentiation by activating FGFR1 in a bFGF-dependent manner. J. Cell Sci. 124(14):2389-400; 1Contributed equally
Sorci G.1, Giovannini G.1, Riuzzi F., Bonifazi P., Zelante T., Zagarella S., Bistoni F., Donato R. and Romani L. (2011) The danger signal S100B integrates pathogen– and danger–sensing pathways to restrain inflammation. PLoS Pathog. 7(3):e1001315; 1Contributed equally
Beccafico S., Riuzzi F., Puglielli C., Mancinelli R., Fulle S., Sorci G. and Donato R. (2011) Human muscle satellite cells show age-related differential expression of S100B protein and RAGE. Age(Dordr) 33:523–541 (DOI 10.1007/s11357-010-9197-x)
Sorci G., Riuzzi F., Arcuri C., Bianchi R., Brozzi F., Tubaro C., Giambanco I. and Donato R. (2010) The many faces of S100B protein: when an extracellular factor inactivates its own receptor and activates another one. Italian J. Anat. Embryol. 115, 1:1/2 (Suppl.)
Danieli-Betto D., Peron S., Germinario E., Zanin M., Sorci G., Franzoso S., Sandonà D., and Betto R. (2010) Sphingosine 1-phosphate signaling is involved in skeletal muscle regeneration. Am. J. Physiol. – Cell Physiol. 298(3):C550-8
Donato R., Sorci G., Riuzzi F., Arcuri C., Bianchi R., Brozzi F., Tubaro C. and Giambanco I. (2009) S100B’s double life: Intracellular regulator and extracellular signal. Biochim. Biophys. Acta – Mol. Cell Res. 1793:1008–1022
Riuzzi F.1, Sorci G.1 and Donato R. (2007) RAGE expression in rhabdomyosarcoma cells results in myogenic differentiation and reduced proliferation, migration, invasiveness, and tumor growth. Am. J. Pathol. 171(3):947-961; 1 Contributed equally
Riuzzi F.1, Sorci G.1 and Donato R. (2006) The amphoterin (HMGB1)/receptor for advanced glycation end products (RAGE) pair modulates myoblast proliferation, apoptosis, adhesiveness, migration and invasiveness. Functional inactivation of RAGE in L6 myoblasts results in tumor formation in vivo. J. Biol. Chem. 281(12):8242-8253; 1 Contributed equally
Riuzzi F.1, Sorci G.1 and Donato R. (2006) S100B Stimulates Myoblast Proliferation and Inhibits Myoblast Differentiation by Independently Stimulating ERK1/2 and Inhibiting p38 MAPK. J. Cell. Physiol. 207:461-470; 1 Contributed equally
Businaro R., Leone S., Fabrizi C., Sorci G., Donato R., Lauro G.M. and Fumagalli L. (2006) S100B Protects LAN-5 Neuroblastoma Cells Against Aβ Amyloid Neurotoxicity Via RAGE Engagement at Low Doses But Increases Aβ Amyloid Neurotoxicity at High Doses. J. Neurosci. Res. 83:897-906
Sorci G., Riuzzi F., and Donato R. (2004) Amphoterin Stimulates Myogenesis and Counteracts the Anti-myogenic Factors Basic Fibroblast Growth Factor and S100B via RAGE Binding. Mol. Cell. Biol. 24(11):4880-4894
Sorci G., Riuzzi F., Agneletti A.L., Marchetti C. and Donato R. (2003) S100B inhibits myogenic differentiation and myotube formation in a RAGE-independent manner. Mol. Cell. Biol. 23(14):4870-4881
Rambotti M.G., Spreca A., Giambanco I., Sorci G., and Donato R. (2002) Ultracytochemistry as a tool for the study of the cellular and subcellular localization of membrane-bound guanylate cyclase (GC) activity. Applicability to both receptor-activated and receptor-independent GC activity. Mol. Cell. Biochem. 230:85-96
Adami C.1, Sorci G.1, Blasi E., Agneletti A.L., Bistoni F., and Donato R. (2001) S100B expression in and effects on microglia. Glia 33(2):131-142 ; 1 Contributed equally
Huttunen H.J., Kuja-Panula J., Sorci G., Agneletti A.L., Donato R., and Rauvala H. (2000) Coregulation of neurite outgrowth and cell survival by amphoterin and S100 proteins through RAGE activation. J. Biol. Chem. 275:40096-40105
Sorci G., Agneletti A.L., and Donato R. (2000) Effects of S100A1 and S100B on microtubule stability. An in vitro study using triton-cytoskeletons from astrocyte and myoblast cell lines. Neuroscience 99:773-783
Rende M., Brizi E., Sorci G., Bianchi R., Provenzano C., Bruno R., and Donato R. (1999) Regulation of the p75 neurotrophin receptor in a rat myogenic cell line (L6). Histochem. J. 31:589-601
Garbuglia M., Verzini M., Sorci G., Bianchi R., Giambanco I., Agneletti A.L., and Donato R. (1999) The calcium-modulated proteins, S100A1 and S100B, as potential regulators of the dynamics of type III intermediate filaments. Braz. J. Med. Biol. Res. 32:1177-1185
Sorci G., Bianchi R., Giambanco I., Rambotti M.G., and Donato R. (1999) Replicating myoblasts and fused myotubes express the calcium-regulated proteins S100A1 and S100B. Cell Calcium 25(2):93-106
Contact
Prof. Guglielmo Sorci
Sect. Anatomy, Dept. Medicine & Surgery
University of Perugia
P.zza Lucio Severi 1, Bld. D, 1st Floor
06132 Perugia PG, Italy
Tel. +39-075-5858258
