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Article

Sertoli Cells Improve Myogenic Differentiation, Reduce Fibrogenic Markers, and Induce Utrophin Expression in Human DMD Myoblasts

1
Department of Translational Medicine, University of Piemonte Orientale, 28100 Novara, Italy
2
Interuniversity Institute of Myology (IIM), 06132 Perugia, Italy
3
Department of Medicine and Surgery, University of Perugia, 06132 Perugia, Italy
4
Consorzio Interuniversitario Biotecnologie (CIB), 34127 Trieste, Italy
5
Centro Biotecnologico Internazionale di Ricerca Traslazionale ad Indirizzo Endocrino, Metabolico ed Embrio-Riproduttivo (CIRTEMER), 06132 Perugia, Italy
6
Centro Universitario di Ricerca sulla Genomica Funzionale (CURGeF), 06132 Perugia, Italy
*
Authors to whom correspondence should be addressed.
These authors contributed equally.
Academic Editor: Jingsong Zhou
Biomolecules 2021, 11(10), 1504; https://doi.org/10.3390/biom11101504
Received: 15 July 2021 / Revised: 5 October 2021 / Accepted: 8 October 2021 / Published: 12 October 2021
(This article belongs to the Section Molecular Medicine)
Duchenne muscular dystrophy (DMD) is an X-linked disease caused by mutations in DMD gene translating in lack of functional dystrophin and resulting in susceptibility of myofibers to rupture during contraction. Inflammation and fibrosis are critical hallmarks of DMD muscles, which undergo progressive degeneration leading to loss of independent ambulation in childhood and death by early adulthood. We reported that intraperitoneal injection of microencapsulated Sertoli cells (SeC) in dystrophic mice translates into recovery of muscle morphology and performance thanks to anti-inflammatory effects and induction of the dystrophin paralogue, utrophin at the muscle level, opening new avenues in the treatment of DMD. The aim of this study is to obtain information about the direct effects of SeC on myoblasts/myotubes, as a necessary step in view of a translational application of SeC-based approaches to DMD. We show that (i) SeC-derived factors stimulate cell proliferation in the early phase of differentiation in C2C12, and human healthy and DMD myoblasts; (ii) SeC delay the expression of differentiation markers in the early phase nevertheless stimulating terminal differentiation in DMD myoblasts; (iii) SeC restrain the fibrogenic potential of fibroblasts, and inhibit myoblast-myofibroblast transdifferentiation; and, (iv) SeC provide functional replacement of dystrophin in preformed DMD myotubes regardless of the mutation by inducing heregulin β1/ErbB2/ERK1/2-dependent utrophin expression. Altogether, these results show that SeC are endowed with promyogenic and antifibrotic effects on dystrophic myoblasts, further supporting their potential use in the treatment of DMD patients. Our data also suggest that SeC-based approaches might be useful in improving the early phase of muscle regeneration, during which myoblasts have to adequately proliferate to replace the damaged muscle mass. View Full-Text
Keywords: duchenne muscular dystrophy (DMD); Sertoli cell; utrophin; heregulin β1; myoblast differentiation; fibrosis; myofibroblast transdifferentiation duchenne muscular dystrophy (DMD); Sertoli cell; utrophin; heregulin β1; myoblast differentiation; fibrosis; myofibroblast transdifferentiation
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MDPI and ACS Style

Salvadori, L.; Chiappalupi, S.; Arato, I.; Mancuso, F.; Calvitti, M.; Marchetti, M.C.; Riuzzi, F.; Calafiore, R.; Luca, G.; Sorci, G. Sertoli Cells Improve Myogenic Differentiation, Reduce Fibrogenic Markers, and Induce Utrophin Expression in Human DMD Myoblasts. Biomolecules 2021, 11, 1504. https://doi.org/10.3390/biom11101504

AMA Style

Salvadori L, Chiappalupi S, Arato I, Mancuso F, Calvitti M, Marchetti MC, Riuzzi F, Calafiore R, Luca G, Sorci G. Sertoli Cells Improve Myogenic Differentiation, Reduce Fibrogenic Markers, and Induce Utrophin Expression in Human DMD Myoblasts. Biomolecules. 2021; 11(10):1504. https://doi.org/10.3390/biom11101504

Chicago/Turabian Style

Salvadori, Laura, Sara Chiappalupi, Iva Arato, Francesca Mancuso, Mario Calvitti, Maria C. Marchetti, Francesca Riuzzi, Riccardo Calafiore, Giovanni Luca, and Guglielmo Sorci. 2021. "Sertoli Cells Improve Myogenic Differentiation, Reduce Fibrogenic Markers, and Induce Utrophin Expression in Human DMD Myoblasts" Biomolecules 11, no. 10: 1504. https://doi.org/10.3390/biom11101504

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