ALESSANDRA RENZINI

Dottoressa di ricerca

ciclo: XXXIII


supervisore: Dott.ssa Viviana Moresi

Titolo della tesi: Unveiling Histone Deacetylase 4 multiple functions in dystrophic skeletal muscle

Histone deacetylase 4 (HDAC4) is a stress-responsive epigenetic factor able to mediate multiple cellular responses in skeletal muscle, upon different pathological conditions. The cytoplasmic functions of HDAC4 in skeletal muscle are poorly characterized so far. HDAC4 expression is upregulated in skeletal muscles of mdx mice, a mouse model for studying Duchenne Muscular Dystrophy (DMD), suggesting a role in this disease. DMD is a genetic, progressive disorder, characterized by muscle degeneration and weakness, ultimately leading to the premature death of patients. Pan-HDAC inhibitors are presently in clinical trial for the treatment of DMD, preventing fibrosis and adipogenesis and promoting compensatory regeneration, despite presenting several important limitations. The identification of the specific functions of different HDAC members is a prerequisite for the development of more selective drugs for the treatment of DMD. With the aim to clarify HDAC4 functions in DMD, we generated dystrophic mice with a skeletal muscle-specific deletion of HDAC4 (mdx;HDAC4mKO mice). Deletion of HDAC4 in skeletal muscle worsens the pathological features of DMD, increasing muscle damage and compromising muscle regeneration and function. HDAC4 affected Fibro Adipogenic Progenitors potential and decreased their ability to support mdx satellite cells, in addition to compromise mdx satellite cell differentiation via paracrine signals. Moreover, HDAC4 orchestrates membrane repair mechanism in mdx muscles and satellite cells, affecting muscle necrosis, satellite cell survival and myogenic capacity. Importantly, ectopic expression of Trim72, a major player in the membrane repair mechanism, or cytoplasmic HDAC4 rescues mdx;HDAC4mKO mice phenotype in vitro and in vivo. We demonstrated that HDAC4 cytoplasmic functions are independent of its deacetylase activity and crucial for allowing a proper response to muscle damage and preserving muscle homeostasis in DMD context. These findings should be considered for future therapeutic approaches.

Produzione scientifica

11573/1711657 - 2024 - Characterization of patient-derived intestinal organoids for modelling fibrosis in Inflammatory bowel disease
Laudadio, Ilaria; Carissimi, Claudia; Scafa, Noemi; Bastianelli, Alex; Fulci, Valerio; Renzini, Alessandra; Russo, Giusy; Oliva, Salvatore; Vitali, Roberta; Palone, Francesca; Cucchiara, Salvatore; Stronati, Laura - 01a Articolo in rivista
rivista: INFLAMMATION RESEARCH (Birkhaeuser Verlag AG:Viaduktstrasse 42-44, CH 4051 Basel Switzerland:011 41 61 2050707, EMAIL: subscriptions@birkhauser.ch, INTERNET: http://www.birkhauser.ch, Fax: 011 41 61 2050792) pp. - - issn: 1023-3830 - wos: WOS:001243266700002 (0) - scopus: 2-s2.0-85195209644 (1)

11573/1675142 - 2023 - Sex differences in inflammation and muscle wasting in aging and disease
Della Peruta, Chiara; Lozanoska Ochser, Biliana; Renzini, Alessandra; Moresi, Viviana; Sanchez Riera, Carles; Bouche', Marina; Coletti, Dario - 01g Articolo di rassegna (Review)
rivista: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (Basel: MDPI Center) pp. 1-20 - issn: 1422-0067 - wos: WOS:000947676400001 (19) - scopus: 2-s2.0-85149851280 (25)

11573/1681346 - 2023 - Histone deacetylases: molecular mechanisms and therapeutic implications for muscular dystrophies
Sandonà, Martina; Cavioli, Giorgia; Renzini, Alessandra; Cedola, Alessia; Gigli, Giuseppe; Coletti, Dario; Mckinsey, Timothy A.; Moresi, Viviana; Saccone, Valentina - 01g Articolo di rassegna (Review)
rivista: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (Basel: MDPI Center) pp. 1-29 - issn: 1422-0067 - wos: WOS:000947327500001 (15) - scopus: 2-s2.0-85149833318 (17)

11573/1670768 - 2022 - PGC-1α in the myofibers regulates the balance between myogenic and adipogenic progenitors affecting muscle regeneration
Beltrà, Marc; Pin, Fabrizio; Costamagna, Domiziana; Duelen, Robin; Renzini, Alessandra; Ballarò, Riccardo; Gracia-Castillo, Lorena; Iannuzzi, Ambra; Moresi, Viviana; Coletti, Dario; Sampaolesi, Maurilio; Penna, Fabio; Costelli, Paola - 01a Articolo in rivista
rivista: ISCIENCE ([Cambridge MA] : Cell Press Elsevier Inc.) pp. 1-19 - issn: 2589-0042 - wos: WOS:000893191200009 (4) - scopus: 2-s2.0-85141805216 (4)

11573/1643002 - 2022 - Determinants of epigenetic resistance to HDAC inhibitors in dystrophic fibro-adipogenic progenitors
Consalvi, S.; Tucciarone, L.; Macri, E.; De Bardi, M.; Picozza, M.; Salvatori, I.; Renzini, A.; Valente, S.; Mai, A.; Moresi, V.; Puri, P. L. - 01a Articolo in rivista
rivista: EMBO REPORTS (Oxford : Oxford University Press, 2000-) pp. 1-19 - issn: 1469-221X - wos: WOS:000778177100001 (9) - scopus: 2-s2.0-85127391022 (8)

11573/1662908 - 2022 - Spatially resolved transcriptomics reveals innervation-responsive functional clusters in skeletal muscle
D'ercole, Chiara; D'angelo, Paolo; Ruggieri, Veronica; Proietti, Daisy; Virtanen, Laura; Parisi, Cristina; Riera, Carles Sanchez; Renzini, Alessandra; Macone, Alberto; Marzullo, Marta; Ciapponi, Laura; Bonvissuto, Davide; Sette, Claudio; Giordani, Lorenzo; Madaro, Luca - 01a Articolo in rivista
rivista: CELL REPORTS (Elsevier B.V. Cambridge MA: Cell Press) pp. 1-23 - issn: 2211-1247 - wos: WOS:000912450400001 (13) - scopus: 2-s2.0-85144347410 (13)

11573/1677241 - 2022 - The RNA helicase DDX5 cooperates with EHMT2 to sustain alveolar rhabdomyosarcoma growth
Gualtieri, Alberto; Bianconi, Valeria; Renzini, Alessandra; Pieroni, Luisa; Licursi, Valerio; Mozzetta, Chiara - 01a Articolo in rivista
rivista: CELL REPORTS (Elsevier B.V. Cambridge MA: Cell Press) pp. - - issn: 2211-1247 - wos: WOS:000875166100001 (5) - scopus: 2-s2.0-85137058763 (5)

11573/1670764 - 2022 - Functional nutrients to ameliorate neurogenic muscle atrophy
Moresi, Viviana; Renzini, Alessandra; Cavioli, Giorgia; Seelaender, Marilia; Coletti, Dario; Gigli, Giuseppe; Cedola, Alessia - 01g Articolo di rassegna (Review)
rivista: METABOLITES (Basel : MDPI) pp. 1-24 - issn: 2218-1989 - wos: WOS:000912422700001 (2) - scopus: 2-s2.0-85149510131 (2)

11573/1640155 - 2022 - Histone deacetylases as modulators of the crosstalk between skeletal muscle and other organs
Renzini, A.; D'onghia, M.; Coletti, D.; Moresi, V. - 01g Articolo di rassegna (Review)
rivista: FRONTIERS IN PHYSIOLOGY (Lausanne: Frontiers Research Foundation, 2010-) pp. 1-15 - issn: 1664-042X - wos: WOS:000768044300001 (9) - scopus: 2-s2.0-85125848360 (10)

11573/1614439 - 2022 - Cytoplasmic HDAC4 regulates the membrane repair mechanism in Duchenne muscular dystrophy
Renzini, A.; Marroncelli, N.; Cavioli, G.; Di Francescantonio, S.; Forcina, L.; Lambridis, A.; Di Giorgio, E.; Valente, S.; Mai, A.; Brancolini, C.; Giampietri, C.; Magenta, A.; De Santa, F.; Adamo, S.; Coletti, D.; Moresi, V. - 01a Articolo in rivista
rivista: JOURNAL OF CACHEXIA, SARCOPENIA AND MUSCLE (Heidelberg ; Berlin : Springer) pp. 1339-1359 - issn: 2190-5991 - wos: WOS:000755498900001 (11) - scopus: 2-s2.0-85124595217 (10)

11573/1670763 - 2022 - Sex and HDAC4 differently affect the pathophysiology of amyotrophic lateral sclerosis in SOD1-G93A mice
Renzini, Alessandra; Pigna, Eva; Rocchi, Marco; Cedola, Alessia; Gigli, Giuseppe; Moresi, Viviana; Coletti, Dario - 01a Articolo in rivista
rivista: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (Basel (Matthaeustrasse 11) : Molecular Diversity Preservation International MDPI) pp. 1-12 - issn: 1661-6596 - wos: WOS:000908636600001 (4) - scopus: 2-s2.0-85145895273 (4)

11573/1571223 - 2021 - Metabolic remodeling in skeletal muscle atrophy as a therapeutic target
Renzini, A.; Riera, C. S.; Minic, I.; D'ercole, C.; Lozanoska-Ochser, B.; Cedola, A.; Gigli, G.; Moresi, V.; Madaro, L. - 01g Articolo di rassegna (Review)
rivista: METABOLITES (Basel : MDPI) pp. 1-26 - issn: 2218-1989 - wos: WOS:000689610600001 (6) - scopus: 2-s2.0-85112434786 (6)

11573/1678492 - 2021 - Metabolic remodeling in skeletal muscle atrophy as a therapeutic target
Renzini, Alessandra; Riera, Carles Sánchez; Minic, Isidora; D'ercole, Chiara; Lozanoska-Ochser, Biliana; Cedola, Alessia; Gigli, Giuseppe; Moresi, Viviana; Madaro, Luca - 01g Articolo di rassegna (Review)
rivista: METABOLITES (Basel : MDPI) pp. 1-26 - issn: 2218-1989 - wos: WOS:000689610600001 (6) - scopus: 2-s2.0-85112434786 (6)

11573/1413912 - 2020 - Neurohypophyseal hormones and skeletal muscle: a tale of two faces
Benoni, Alexandra Auriane Patricia; Renzini, Alessandra; Cavioli, Giorgia; Adamo, Sergio - 01a Articolo in rivista
rivista: EUROPEAN JOURNAL OF TRANSLATIONAL MYOLOGY (- Padova : Pagepress -Padova : Unipress) pp. 53-57 - issn: 2037-7460 - wos: WOS:000566757600004 (1) - scopus: 2-s2.0-85089598672 (1)

11573/1327996 - 2019 - Interplay between metabolites and the epigenome in regulating embryonic and adult stem cell potency and maintenance
Harvey, A.; Caretti, G.; Moresi, V.; Renzini, A.; Adamo, S. - 01g Articolo di rassegna (Review)
rivista: STEM CELL REPORTS (Amsterdam : Elsevier) pp. 573-589 - issn: 2213-6711 - wos: WOS:000489322400001 (33) - scopus: 2-s2.0-85072285149 (37)

11573/1361417 - 2019 - Metabolic control of muscle stem cells
Renzini, Alessandra; Adamo, Sergio; Moresi, Viviana - 01a Articolo in rivista
rivista: ORGANISMS (Roma: Sapienza Università di Roma) pp. 24-35 - issn: 2532-5876 - wos: (0) - scopus: (0)

11573/1669800 - 2019 - Thyroid hormone protects from fasting-induced skeletal muscle atrophy by promoting metabolic adaptation
Ucci, Sarassunta; Renzini, Alessandra; Russi, Valentina; Mangialardo, Claudia; Cammarata, Ilenia; Cavioli, Giorgia; Giulia Santaguida, Maria; Virili, Camilla; Centanni, Marco; Adamo, Sergio; Moresi, Viviana; Verga Falzacappa, Cecilia - 01a Articolo in rivista
rivista: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (Basel: MDPI Center) pp. 1-21 - issn: 1422-0067 - wos: WOS:000502786800236 (12) - scopus: 2-s2.0-85075064731 (11)

11573/1103599 - 2018 - HDAC4 preserves skeletal muscle structure following long-term denervation by mediating distinct cellular responses
Pigna, Eva; Renzini, Alessandra; Greco, Emanuela; Simonazzi, Elena; Fulle, Stefania; Mancinelli, Rosa; Moresi, Viviana; Adamo, Sergio - 01a Articolo in rivista
rivista: SKELETAL MUSCLE (London : BioMed Central) pp. 1-16 - issn: 2044-5040 - wos: WOS:000426511000001 (24) - scopus: 2-s2.0-85042585773 (23)

11573/1116740 - 2018 - Culture conditions influence satellite cell activation and survival of single myofibers
Renzini, Alessandra; Benedetti, Anna; Bouche', Marina; Silvestroni, Leopoldo; Adamo, Sergio; Moresi, Viviana - 01a Articolo in rivista
rivista: EUROPEAN JOURNAL OF TRANSLATIONAL MYOLOGY (- Padova : Pagepress -Padova : Unipress) pp. 167-174 - issn: 2037-7460 - wos: WOS:000455714800003 (13) - scopus: 2-s2.0-85057973341 (12)

11573/1141812 - 2018 - HDAC4 regulates skeletal muscle regeneration via soluble factors
Renzini, Alessandra; Marroncelli, Nicoletta; Noviello, Chiara; Moresi, Viviana; Adamo, Sergio - 01a Articolo in rivista
rivista: FRONTIERS IN PHYSIOLOGY (Lausanne: Frontiers Research Foundation, 2010-) pp. 1-11 - issn: 1664-042X - wos: WOS:000445795300001 (16) - scopus: 2-s2.0-85071195714 (18)

11573/957786 - 2017 - Coordinated actions of microRNAs with other epigenetic factors regulate skeletal muscle development and adaptation
Bianchi, Marzia; Renzini, Alessandra; Adamo, Sergio; Moresi, Viviana - 01g Articolo di rassegna (Review)
rivista: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (Basel: MDPI Center) pp. 1-14 - issn: 1422-0067 - wos: WOS:000402639400164 (47) - scopus: 2-s2.0-85018527176 (64)

© Università degli Studi di Roma "La Sapienza" - Piazzale Aldo Moro 5, 00185 Roma