Selective Inhibition of Genomic and Non-Genomic Effects of Thyroid Hormone Regulates Muscle Cell Differentiation and Metabolic Behavior
Thyroid hormones (THs) are key regulators of different biological processes. Their action involves genomic and non-genomic mechanisms, which together mediate the final effects of TH in target tissues. However, the proportion of the two processes and their contribution to the TH-mediated effects are...
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MDPI AG
2021-07-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/13/7175 |
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| author | Annarita Nappi Melania Murolo Serena Sagliocchi Caterina Miro Annunziata Gaetana Cicatiello Emery Di Cicco Rossella Di Paola Maddalena Raia Lucia D’Esposito Mariano Stornaiuolo Monica Dentice |
| author_facet | Annarita Nappi Melania Murolo Serena Sagliocchi Caterina Miro Annunziata Gaetana Cicatiello Emery Di Cicco Rossella Di Paola Maddalena Raia Lucia D’Esposito Mariano Stornaiuolo Monica Dentice |
| author_sort | Annarita Nappi |
| collection | DOAJ |
| description | Thyroid hormones (THs) are key regulators of different biological processes. Their action involves genomic and non-genomic mechanisms, which together mediate the final effects of TH in target tissues. However, the proportion of the two processes and their contribution to the TH-mediated effects are still poorly understood. Skeletal muscle is a classical target tissue for TH, which regulates muscle strength and contraction, as well as energetic metabolism of myofibers. Here we address the different contribution of genomic and non-genomic action of TH in skeletal muscle cells by specifically silencing the deiodinase <i>Dio2</i> or the <i>β3-Integrin</i> expression via CRISPR/Cas9 technology. We found that myoblast proliferation is inversely regulated by integrin signal and the D2-dependent TH activation. Similarly, inhibition of the nuclear receptor action reduced myoblast proliferation, confirming that genomic action of TH attenuates proliferative rates. Contrarily, genomic and non-genomic signals promote muscle differentiation and the regulation of the redox state. Taken together, our data reveal that integration of genomic and non-genomic signal pathways finely regulates skeletal muscle physiology. These findings not only contribute to the understanding of the mechanisms involved in TH modulation of muscle physiology but also add insight into the interplay between different mechanisms of action of TH in muscle cells. |
| first_indexed | 2024-03-10T09:51:31Z |
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| id | doaj.art-1d1fb75a70ab4a50b8b4dca89398527d |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T09:51:31Z |
| publishDate | 2021-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-1d1fb75a70ab4a50b8b4dca89398527d2023-11-22T02:41:32ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-07-012213717510.3390/ijms22137175Selective Inhibition of Genomic and Non-Genomic Effects of Thyroid Hormone Regulates Muscle Cell Differentiation and Metabolic BehaviorAnnarita Nappi0Melania Murolo1Serena Sagliocchi2Caterina Miro3Annunziata Gaetana Cicatiello4Emery Di Cicco5Rossella Di Paola6Maddalena Raia7Lucia D’Esposito8Mariano Stornaiuolo9Monica Dentice10Department of Clinical Medicine and Surgery, University of Naples Federico II, 80131 Naples, ItalyDepartment of Clinical Medicine and Surgery, University of Naples Federico II, 80131 Naples, ItalyDepartment of Clinical Medicine and Surgery, University of Naples Federico II, 80131 Naples, ItalyDepartment of Clinical Medicine and Surgery, University of Naples Federico II, 80131 Naples, ItalyDepartment of Clinical Medicine and Surgery, University of Naples Federico II, 80131 Naples, ItalyDepartment of Clinical Medicine and Surgery, University of Naples Federico II, 80131 Naples, ItalyDepartment of Clinical Medicine and Surgery, University of Naples Federico II, 80131 Naples, ItalyCEINGE–Biotecnologie Avanzate Scarl, 80131 Naples, ItalyCentro Servizi Veterinari, University of Naples Federico II, 80131 Naples, ItalyDepartment of Pharmacy, University of Naples Federico II, 80131 Naples, ItalyDepartment of Clinical Medicine and Surgery, University of Naples Federico II, 80131 Naples, ItalyThyroid hormones (THs) are key regulators of different biological processes. Their action involves genomic and non-genomic mechanisms, which together mediate the final effects of TH in target tissues. However, the proportion of the two processes and their contribution to the TH-mediated effects are still poorly understood. Skeletal muscle is a classical target tissue for TH, which regulates muscle strength and contraction, as well as energetic metabolism of myofibers. Here we address the different contribution of genomic and non-genomic action of TH in skeletal muscle cells by specifically silencing the deiodinase <i>Dio2</i> or the <i>β3-Integrin</i> expression via CRISPR/Cas9 technology. We found that myoblast proliferation is inversely regulated by integrin signal and the D2-dependent TH activation. Similarly, inhibition of the nuclear receptor action reduced myoblast proliferation, confirming that genomic action of TH attenuates proliferative rates. Contrarily, genomic and non-genomic signals promote muscle differentiation and the regulation of the redox state. Taken together, our data reveal that integration of genomic and non-genomic signal pathways finely regulates skeletal muscle physiology. These findings not only contribute to the understanding of the mechanisms involved in TH modulation of muscle physiology but also add insight into the interplay between different mechanisms of action of TH in muscle cells.https://www.mdpi.com/1422-0067/22/13/7175thyroid hormonegenomic and non-genomic actiondeiodinase |
| spellingShingle | Annarita Nappi Melania Murolo Serena Sagliocchi Caterina Miro Annunziata Gaetana Cicatiello Emery Di Cicco Rossella Di Paola Maddalena Raia Lucia D’Esposito Mariano Stornaiuolo Monica Dentice Selective Inhibition of Genomic and Non-Genomic Effects of Thyroid Hormone Regulates Muscle Cell Differentiation and Metabolic Behavior International Journal of Molecular Sciences thyroid hormone genomic and non-genomic action deiodinase |
| title | Selective Inhibition of Genomic and Non-Genomic Effects of Thyroid Hormone Regulates Muscle Cell Differentiation and Metabolic Behavior |
| title_full | Selective Inhibition of Genomic and Non-Genomic Effects of Thyroid Hormone Regulates Muscle Cell Differentiation and Metabolic Behavior |
| title_fullStr | Selective Inhibition of Genomic and Non-Genomic Effects of Thyroid Hormone Regulates Muscle Cell Differentiation and Metabolic Behavior |
| title_full_unstemmed | Selective Inhibition of Genomic and Non-Genomic Effects of Thyroid Hormone Regulates Muscle Cell Differentiation and Metabolic Behavior |
| title_short | Selective Inhibition of Genomic and Non-Genomic Effects of Thyroid Hormone Regulates Muscle Cell Differentiation and Metabolic Behavior |
| title_sort | selective inhibition of genomic and non genomic effects of thyroid hormone regulates muscle cell differentiation and metabolic behavior |
| topic | thyroid hormone genomic and non-genomic action deiodinase |
| url | https://www.mdpi.com/1422-0067/22/13/7175 |
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