GIORGIA CATARINELLA

Dottoressa di ricerca

ciclo: XXXIV


supervisore: Lucia Latella
relatore: Antonio Musarò

Titolo della tesi: Role of STAT3-mediated autophagy in driving muscle regeneration during aging

Age-related reduced regenerative potential and muscle wasting (sarcopenia) has been in part associated with a decline in the number and function of adult muscle stem cells, (MuSCs), due to intrinsic and niche/systemic alterations. We and others have demonstrated a key role of STAT3 in regulating MuSCs expansion and differentiation. In addition, we described the essential role of autophagy in driving MuSCs function toward efficient muscle regeneration. The established role of autophagy in maintaining muscle mass and tissue homeostasis together with the emerging role of STAT3 in regulating the autophagic process inspired the rationale behind this project which resides in the study of the STAT3-mediated autophagy toward skeletal muscle repair. Our hypothesis is that STAT3 might have a role in regulating myogenic lineage and regeneration process by affecting the autophagic process thereby restoring the bioenergetic demand of the old myogenic niche to support muscle regeneration. We show that STAT3 inhibitor (STAT3i) treatment induces the autophagic process upon muscle regeneration both in vitro and in vivo. STAT3-mediated autophagy during muscle regeneration is associated with eIF2𝛼 phosphorylation that is conceivably achieved by PKR that is no longer sequestered by STAT3. Intriguingly, STAT3i treatment is able to resume the autophagic process in old MuSCs, otherwise characterized by low levels of autophagy, leading to proficient muscle regeneration. Our findings highlight the key role of the STAT3-dependent autophagy in driving muscle regeneration, revealing potential biological targets in MuSCs that may restart an efficient regenerative response in aged mice.

Produzione scientifica

11573/1669376 - 2022 - SerpinE1 drives a cell-autonomous pathogenic signaling in Hutchinson-Gilford progeria syndrome
Catarinella, Giorgia; Nicoletti, Chiara; Bracaglia, Andrea; Procopio, Paola; Salvatori, Illari; Taggi, Marilena; Valle, Cristiana; Ferri, Alberto; Canipari, Rita; Puri, Pier Lorenzo; Latella, Lucia - 01a Articolo in rivista
rivista: CELL DEATH & DISEASE (Nature Group) pp. 1-12 - issn: 2041-4889 - wos: WOS:000844980000001 (2) - scopus: 2-s2.0-85137083593 (2)

11573/1668300 - 2021 - Targeting SerpinE1 reverses cellular features of Hutchinson-Gilford progeria syndrome
Catarinella, Giorgia; Nicoletti, Chiara; Bracaglia, Andrea; Procopio, Paola; Salvatori, Illari; Taggi, Marilena; Ferri, Alberto; Valle, Cristiana; Canipari, Rita; Puri, Pier Lorenzo; Latella, Lucia - 01a Articolo in rivista
rivista: CELL DEATH & DISEASE (Nature Group) pp. - - issn: 2041-4889 - wos: (0) - scopus: (0)

11573/1571139 - 2021 - Givinostat as metabolic enhancer reverting mitochondrial biogenesis deficit in Duchenne muscular dystrophy
Giovarelli, M.; Zecchini, S.; Catarinella, G.; Moscheni, C.; Sartori, P.; Barbieri, C.; Roux-Biejat, P.; Napoli, A.; Vantaggiato, C.; Cervia, D.; Perrotta, C.; Clementi, E.; Latella, L.; De Palma, C. - 01a Articolo in rivista
rivista: PHARMACOLOGICAL RESEARCH (Attuale:ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD, 24-28 OVAL RD, LONDON, ENGLAND, NW1 7DX Elsevier Science Limited:Oxford Fulfillment Center, PO Box 800, Kidlington Oxford OX5 1DX United Kingdom:011 44 1865 843000, 011 44 1865 843699, EMAIL: asianfo@elsevier.com, tcb@elsevier.co.UK, INTERNET: http://www.elsevier.com, http://www.elsevier.com/locate/shpsa/, Fax: 011 44 1865 843010) pp. 1-14 - issn: 1043-6618 - wos: WOS:000680035100058 (15) - scopus: 2-s2.0-85108986148 (15)

11573/1616599 - 2021 - Reticulon-1c involvement in muscle regeneration
Rossin, F.; Avitabile, E.; Catarinella, G.; Fornetti, E.; Testa, S.; Oliverio, S.; Gargioli, C.; Cannata, S.; Latella, L.; Di Sano, F. - 01a Articolo in rivista
rivista: METABOLITES (Basel : MDPI) pp. 1-11 - issn: 2218-1989 - wos: WOS:000735984800001 (0) - scopus: 2-s2.0-85121670610 (0)

11573/1292396 - 2018 - Bet on autophagy in the race against muscular dystrophies
Catarinella, G.; Latella, L. - 01m Editorial/Introduzione in rivista
rivista: MUSCLE & NERVE (John Wiley & Sons Incorporated:Customer Service, 111 River Street:Hoboken, NJ 07030:(800)225-5945, (201)748-6000, EMAIL: societyinfo@wiley.com, INTERNET: http://www.wiley.com, Fax: (212)748-6551) pp. 332-334 - issn: 0148-639X - wos: WOS:000444079300004 (0) - scopus: 2-s2.0-85053079108 (0)

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