ALESSANDRA RENZINI

Dottoressa

ciclo: XXXIII


tutor: 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

  • 11573/957786 - 2017 - Coordinated actions of microRNAs with other epigenetic factors regulate skeletal muscle development and adaptation (01g Articolo di rassegna (Review))
    BIANCHI, MARZIA; RENZINI, ALESSANDRA; ADAMO, SERGIO; MORESI, VIVIANA
  • 11573/1116740 - 2018 - Culture conditions influence satellite cell activation and survival of single myofibers (01a Articolo in rivista)
    RENZINI, ALESSANDRA; BENEDETTI, ANNA; BOUCHE', MARINA; SILVESTRONI, LEOPOLDO; ADAMO, SERGIO; MORESI, VIVIANA
  • 11573/1141812 - 2018 - HDAC4 regulates skeletal muscle regeneration via soluble factors (01a Articolo in rivista)
    RENZINI, ALESSANDRA; MARRONCELLI, NICOLETTA; NOVIELLO, CHIARA; MORESI, VIVIANA; ADAMO, SERGIO
  • 11573/1330281 - 2019 - Thyroid Hormone Protects from Fasting-Induced Skeletal Muscle Atrophy by Promoting Metabolic Adaptation (01a Articolo in rivista)
    UCCI, SARASSUNTA; RENZINI, ALESSANDRA; MANGIALARDO, CLAUDIA; CAMMARATA, ILENIA; SANTAGUIDA, MARIA GIULIA; VIRILI, CAMILLA; CENTANNI, MARCO; ADAMO, SERGIO; MORESI, VIVIANA; VERGA FALZACAPPA, CECILIA
  • 11573/1327996 - 2019 - Interplay between metabolites and the epigenome in regulating embryonic and adult stem cell potency and maintenance (01g Articolo di rassegna (Review))
    MORESI, VIVIANA; RENZINI, ALESSANDRA; ADAMO, SERGIO
  • 11573/1361417 - 2019 - Metabolic control of muscle stem cells (01a Articolo in rivista)
    RENZINI, ALESSANDRA; ADAMO, SERGIO; MORESI, VIVIANA
  • 11573/1413912 - 2020 - Neurohypophyseal hormones and skeletal muscle: a tale of two faces (01a Articolo in rivista)
    BENONI, ALEXANDRA AURIANE PATRICIA; RENZINI, ALESSANDRA; ADAMO, SERGIO
  • 11573/1490141 - 2021 - Unveiling Histone Deacetylase 4 multiple functions in dystrophic skeletal muscle (07a Tesi di Dottorato)
    RENZINI, ALESSANDRA
  • 11573/1571223 - 2021 - Metabolic remodeling in skeletal muscle atrophy as a therapeutic target (01g Articolo di rassegna (Review))
    RENZINI, ALESSANDRA; D'ERCOLE, CHIARA; LOZANOSKA OCHSER, BILIANA; CEDOLA, ANDREA; MADARO, LUCA
  • 11573/1103599 - 2018 - HDAC4 preserves skeletal muscle structure following long-term denervation by mediating distinct cellular responses (01a Articolo in rivista)
    PIGNA, EVA; RENZINI, ALESSANDRA; SIMONAZZI, ELENA; MORESI, VIVIANA; ADAMO, SERGIO
  • 11573/1614439 - 2022 - Cytoplasmic HDAC4 regulates the membrane repair mechanism in Duchenne muscular dystrophy (01a Articolo in rivista)
    RENZINI, ALESSANDRA; MARRONCELLI, NICOLETTA; CAVIOLI, GIORGIA; DI FRANCESCANTONIO, SILVIA; FORCINA, LAURA; VALENTE, SERGIO; MAI, ANTONELLO; GIAMPIETRI, CLAUDIA; MAGENTA, ALESSANDRA; DE SANTA, FRANCESCA; ADAMO, SERGIO; COLETTI, DARIO; MORESI, VIVIANA
  • 11573/1643002 - 2022 - Determinants of epigenetic resistance to HDAC inhibitors in dystrophic fibro-adipogenic progenitors (01a Articolo in rivista)
    PICOZZA, MARIA; SALVATORI, ILLARI; RENZINI, ALESSANDRA; MAI, ANTONELLO
  • 11573/1640155 - 2022 - Histone deacetylases as modulators of the crosstalk between skeletal muscle and other organs (01g Articolo di rassegna (Review))
    RENZINI, ALESSANDRA; D'ONGHIA, MARCO; COLETTI, DARIO
  • 11573/1662908 - 2022 - Spatially resolved transcriptomics reveals innervation-responsive functional clusters in skeletal muscle (01a Articolo in rivista)
    D'ANGELO, PAOLO; RUGGIERI, VERONICA; PROIETTI, DAISY; SANCHEZ RIERA, CARLES; RENZINI, ALESSANDRA; MACONE, ALBERTO; MARZULLO, MARTA; CIAPPONI, LAURA; BONVISSUTO, DAVIDE; GIORDANI, LORENZO; MADARO, LUCA
  • 11573/1666373 - 2022 - All-sky search for continuous gravitational waves from isolated neutron stars using Advanced LIGO and Advanced Virgo O3 data (01a Articolo in rivista)
    ASTONE, PIA; BABAK, STANISLAV; BARSUGLIA, MATTEO; BERNUZZI, SEBASTIANO; BHAUMIK, SUDARSHANA; BOSCHI, VITTORIA; BRESCHI, MARCO; BRYANT, JOHN; BUONANNO, ANDREA; CABRAS, GIULIA; CAGNOLI, GIANPIETRO; CANEPA, MAURIZIO; CARBOGNANI, FEDERICO; CASENTINI, CLAUDIO; CHEN, KEFAN; CHEN, ZHIXIONG; CHENG, HAO; CHIARINI, GIULIA; CIANI, GESSICA; CIOLFI, RICCARDO; COLPI, MONICA; COREZZI, SILVIA; DAL CANTON, TITO; DATTA, SAYAK; DE LILLO, FILIPPO; DEL POZZO, WALTER; DI GIROLAMO, TRISTANO; DI PALMA, IRENE; ANELLI, DEBORA; GARUFI, FRANCESCO; GENNAI, ANDREA; GIACOMAZZO, BRUNO; GIACOPPO, LAURA; GHEZZI, CARLA; GRANATA, VERONICA; ANELLI, DEBORA; GUERRA, DAVIDE; HANEY, MARIA; HANNA, CHARLIE; HASKELL, SHAHAR BERTHA; HILL, PHILLIP; HSU, CHING YU; JU, LINGXING; KIMURA, NOBUHIRO; KUMAR, RAHUL; LAZZARO, COSMO ANTONIO; LEACI, PAOLA; LEE, KIERAN JOHN DAVID; LOPEZ, DANIEL FELIPE; LORENZINI, MATTEO; MAJORANA, ETTORE; MAPELLI, MICHELA; MARCHESONI, FABIO; MARTINOVIC, KSENIJA; MASTROGIOVANNI, SIMONE; MCCORMICK, SETH THOMAS; MIANI, ANNA; MICHEL, CECILE; MILLER, JOSHUA BENJAMIN; MONTANI, MARCO; MUCIACCIA, FEDERICO; MUKHERJEE, DEBANGANA; NARDECCHIA, ILARIA; NITOGLIA, ELISA; PAGLIAROLI, GIACOMO; PANNARALE GRECO, FRANCESCO; PAPPAS, GEORGIOS; PATRICELLI, BARBARA; PLACIDI, ERNESTO; POLINI, ELEONORA; PRACCHIA, MATTEO; PUPPO, PATRIZIO MARIA; RAPAGNANI, PIERO; RAZZANO, GUIDO MARIA; REID, SUSAN; RENZINI, ALESSANDRA; RUGGI, PAOLO ALBERTO; SAHA, SUBROTA KUMAR; SINGH, NACHATTER; SORDINI, VIOLA; SUN, LING; TARANTO, CLAUDIA; TOSTA E MELO, IARA; VETRANO, FABIO; WHITE, DAVID GORDON; WU, CHIEN LIN; YAMAMOTO, KAZUHIRO; YANG, LI; ZHANG, LI; ZHANG, TONGBING; ZHOU, ZHANPENG
  • 11573/1666372 - 2022 - Search for gravitational waves from Scorpius X-1 with a hidden Markov model in O3 LIGO data (01a Articolo in rivista)
    ASTONE, PIA; BABAK, STANISLAV; BARSUGLIA, MATTEO; BERNUZZI, SEBASTIANO; BHAUMIK, SUDARSHANA; BOSCHI, VITTORIA; BRESCHI, MARCO; BRYANT, JOHN; BUONANNO, ANDREA; CABRAS, GIULIA; CAGNOLI, GIANPIETRO; CANEPA, MAURIZIO; CARBOGNANI, FEDERICO; CASENTINI, CLAUDIO; CHEN, KEFAN; CHEN, ZHIXIONG; CHENG, HAO; CHIARINI, GIULIA; CIANI, GESSICA; CIOLFI, RICCARDO; COLPI, MONICA; COREZZI, SILVIA; DATTA, SAYAK; DE LILLO, FILIPPO; DEL POZZO, WALTER; DI GIROLAMO, TRISTANO; DI PALMA, IRENE; ANELLI, DEBORA; GARUFI, FRANCESCO; GENNAI, ANDREA; GIACOMAZZO, BRUNO; GIACOPPO, LAURA; GHEZZI, CARLA; GRANATA, VERONICA; ANELLI, DEBORA; GUERRA, DAVIDE; HANEY, MARIA; HANNA, CHARLIE; HASKELL, SHAHAR BERTHA; HILL, PHILLIP; HSU, CHING YU; JU, LINGXING; KIMURA, NOBUHIRO; KUMAR, RAHUL; LAZZARO, COSMO ANTONIO; LEACI, PAOLA; LEE, KIERAN JOHN DAVID; LOPEZ, DANIEL FELIPE; LORENZINI, MATTEO; MAJORANA, ETTORE; MAPELLI, MICHELA; MARCHESONI, FABIO; MARTINOVIC, KSENIJA; MASTROGIOVANNI, SIMONE; MCCORMICK, SETH THOMAS; MIANI, ANNA; MICHEL, CECILE; MILLER, JOSHUA BENJAMIN; MONTANI, MARCO; MUCIACCIA, FEDERICO; MUKHERJEE, DEBANGANA; NARDECCHIA, ILARIA; NITOGLIA, ELISA; PAGLIAROLI, GIACOMO; PANNARALE GRECO, FRANCESCO; PAPPAS, GEORGIOS; PATRICELLI, BARBARA; PLACIDI, ERNESTO; POLINI, ELEONORA; PRACCHIA, MATTEO; PUPPO, PATRIZIO MARIA; RAPAGNANI, PIERO; RAZZANO, GUIDO MARIA; REID, SUSAN; RENZINI, ALESSANDRA; RUGGI, PAOLO ALBERTO; SAHA, SUBROTA KUMAR; SINGH, NACHATTER; SORDINI, VIOLA; SUN, LING; TARANTO, CLAUDIA; VETRANO, FABIO; WU, CHIEN LIN; YAMAMOTO, KAZUHIRO; YANG, LI; ZHANG, LI; ZHANG, TONGBING; ZHOU, ZHANPENG
  • 11573/1666364.3 - 2022 - Model-based Cross-correlation Search for Gravitational Waves from the Low-mass X-Ray Binary Scorpius X-1 in LIGO O3 Data (01a Articolo in rivista)
    ASTONE, PIA; BABAK, STANISLAV; BARISH, BARRY CLARK; BARSUGLIA, MATTEO; BERNUZZI, SEBASTIANO; BHAUMIK, SUDARSHANA; BONAVENA, LUIS DIEGO; BOSCHI, VITTORIA; BRESCHI, MARCO; BRYANT, JOHN; BUONANNO, ANDREA; CABRAS, GIULIA; CAGNOLI, GIANPIETRO; CANEPA, MAURIZIO; CARBOGNANI, FEDERICO; CASENTINI, CLAUDIO; CHEN, KEFAN; CHENG, HAO; CHESSA, PASQUALE; CHIARINI, GIULIA; CIANI, GESSICA; CIOLFI, RICCARDO; COREZZI, SILVIA; COLPI, MONICA; DAL CANTON, TITO; DALL'OSSO, SIMONE; DE LILLO, FILIPPO; DEL POZZO, WALTER; DI GIROLAMO, TRISTANO; DI PALMA, IRENE; ANELLI, DEBORA; GARUFI, FRANCESCO; GENNAI, ANDREA; GHOSH, ANWESHA; GHOSH, ANWESHA; GHOSH, SAJIB; GHOSH, SAJIB; GIACOPPO, LAURA; GHEZZI, CARLA; GRANATA, VERONICA; ANELLI, DEBORA; GUERRA, DAVIDE; GUIDI, GIANLUCA MARIA; GUPTA, ANUPAM; GUPTA, ANUPAM; HANEY, MARIA; HANNA, CHARLIE; HANNAM, MARK DOUGLAS; HASKELL, SHAHAR BERTHA; HILL, PHILLIP; JOHNY, NIXON; JU, LINGXING; KIM, WI SEON; KIMURA, NOBUHIRO; KROLAK, ALEKSANDRA ANNA; LAZZARO, COSMO ANTONIO; LEACI, PAOLA; LEE, KIERAN JOHN DAVID; LONDON, LIONEL TERRELL; LOPEZ, DANIEL FELIPE; LORENZINI, MATTEO; MAJORANA, ETTORE; MAPELLI, MICHELA; MARCHESONI, FABIO; MARTINOVIC, KSENIJA; MASTROGIOVANNI, SIMONE; MCCORMICK, SETH THOMAS; MIANI, ANNA; MICHEL, CECILE; MILLER, ANDREW LAWRENCE; MILLER, JOSHUA BENJAMIN; MENNEA, LUCIA MIR; MONTANI, MARCO; MUCIACCIA, FEDERICO; MUKHERJEE, DEBANGANA; NARDECCHIA, ILARIA; NITOGLIA, ELISA; NOVAK, JAN; OERTEL, MICHAEL; PAGLIAROLI, GIACOMO; PANNARALE GRECO, FRANCESCO; PAPPAS, GEORGIOS; PATRICELLI, BARBARA; PICCINNI, ORNELLA JULIANA; PLACIDI, ERNESTO; POLINI, ELEONORA; PRACCHIA, MATTEO; PUPPO, PATRIZIO MARIA; RAPAGNANI, PIERO; RAZZANO, GUIDO MARIA; REID, SUSAN; RENZINI, ALESSANDRA; ROSSELLO, MARIO; RUGGI, PAOLO ALBERTO; SAHA, SUBROTA KUMAR; SINGH, NACHATTER; SORDINI, VIOLA; SUN, LING; SUZUKI, TAKASHI; SUZUKI, TAKASHI; SUZUKI, TAKASHI; TANAKA, TOMOKO; TANAKA, TOMOKO; TARANTO, CLAUDIA; TOSTA E MELO, IARA; VETRANO, FABIO; YIP, WANG HON; WU, CHIEN LIN; YAMAMOTO, KAZUHIRO; YANG, LI; ZHANG, LI; ZHANG, TONGBING; ZHENG, YAN

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