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Lack of PKCθ Promotes Regenerative Ability of Muscle Stem Cells in Chronic Muscle Injury.
Int J Mol Sci. 2020 Jan 31; 21(3)IJ

Abstract

Duchenne muscular dystrophy (DMD) is a genetic disease characterized by muscle wasting and chronic inflammation, leading to impaired satellite cells (SCs) function and exhaustion of their regenerative capacity. We previously showed that lack of PKCθ in mdx mice, a mouse model of DMD, reduces muscle wasting and inflammation, and improves muscle regeneration and performance at early stages of the disease. In this study, we show that muscle regeneration is boosted, and fibrosis reduced in mdxθ-/- mice, even at advanced stages of the disease. This phenotype was associated with a higher number of Pax7 positive cells in mdxθ-/- muscle compared with mdx muscle, during the progression of the disease. Moreover, the expression level of Pax7 and Notch1, the pivotal regulators of SCs self-renewal, were upregulated in SCs isolated from mdxθ-/- muscle compared with mdx derived SCs. Likewise, the expression of the Notch ligands Delta1 and Jagged1 was higher in mdxθ-/- muscle compared with mdx. The expression level of Delta1 and Jagged1 was also higher in PKCθ-/- muscle compared with WT muscle following acute injury. In addition, lack of PKCθ prolonged the survival and sustained the differentiation of transplanted myogenic progenitors. Overall, our results suggest that lack of PKCθ promotes muscle repair in dystrophic mice, supporting stem cells survival and maintenance through increased Delta-Notch signaling.

Authors+Show Affiliations

Department of AHFMO, University of Rome "la Sapienza", Via A. Scarpa 14, 00161 Rome, Italy.Department of AHFMO, University of Rome "la Sapienza", Via A. Scarpa 14, 00161 Rome, Italy.Department of AHFMO, University of Rome "la Sapienza", Via A. Scarpa 14, 00161 Rome, Italy. IRCCS Fondazione Santa Lucia (FSL), 00143 Rome, Italy.Department of AHFMO, University of Rome "la Sapienza", Via A. Scarpa 14, 00161 Rome, Italy. IRCCS Fondazione Santa Lucia (FSL), 00143 Rome, Italy.IRCCS Fondazione Santa Lucia (FSL), 00143 Rome, Italy.IRCCS Fondazione Santa Lucia (FSL), 00143 Rome, Italy. Department of Life Sciences and Public Health, Università Cattolica del Sacro Cuore, 00168 Rome, Italy.Development, Aging and Regeneration Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA.Department of Biology, Tor Vergata University, 00133 Rome, Italy.Department of AHFMO, University of Rome "la Sapienza", Via A. Scarpa 14, 00161 Rome, Italy.Department of AHFMO, University of Rome "la Sapienza", Via A. Scarpa 14, 00161 Rome, Italy.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32023816

Citation

Fiore, Piera Filomena, et al. "Lack of PKCθ Promotes Regenerative Ability of Muscle Stem Cells in Chronic Muscle Injury." International Journal of Molecular Sciences, vol. 21, no. 3, 2020.
Fiore PF, Benedetti A, Sandonà M, et al. Lack of PKCθ Promotes Regenerative Ability of Muscle Stem Cells in Chronic Muscle Injury. Int J Mol Sci. 2020;21(3).
Fiore, P. F., Benedetti, A., Sandonà, M., Madaro, L., De Bardi, M., Saccone, V., Puri, P. L., Gargioli, C., Lozanoska-Ochser, B., & Bouché, M. (2020). Lack of PKCθ Promotes Regenerative Ability of Muscle Stem Cells in Chronic Muscle Injury. International Journal of Molecular Sciences, 21(3). https://doi.org/10.3390/ijms21030932
Fiore PF, et al. Lack of PKCθ Promotes Regenerative Ability of Muscle Stem Cells in Chronic Muscle Injury. Int J Mol Sci. 2020 Jan 31;21(3) PubMed PMID: 32023816.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Lack of PKCθ Promotes Regenerative Ability of Muscle Stem Cells in Chronic Muscle Injury. AU - Fiore,Piera Filomena, AU - Benedetti,Anna, AU - Sandonà,Martina, AU - Madaro,Luca, AU - De Bardi,Marco, AU - Saccone,Valentina, AU - Puri,Pier Lorenzo, AU - Gargioli,Cesare, AU - Lozanoska-Ochser,Biliana, AU - Bouché,Marina, Y1 - 2020/01/31/ PY - 2020/01/07/received PY - 2020/01/24/revised PY - 2020/01/29/accepted PY - 2020/2/7/entrez PY - 2020/2/7/pubmed PY - 2020/11/18/medline KW - Duchenne Muscular Dystrophy KW - Protein Kinase C θ KW - mdx KW - muscle satellite cells JF - International journal of molecular sciences JO - Int J Mol Sci VL - 21 IS - 3 N2 - Duchenne muscular dystrophy (DMD) is a genetic disease characterized by muscle wasting and chronic inflammation, leading to impaired satellite cells (SCs) function and exhaustion of their regenerative capacity. We previously showed that lack of PKCθ in mdx mice, a mouse model of DMD, reduces muscle wasting and inflammation, and improves muscle regeneration and performance at early stages of the disease. In this study, we show that muscle regeneration is boosted, and fibrosis reduced in mdxθ-/- mice, even at advanced stages of the disease. This phenotype was associated with a higher number of Pax7 positive cells in mdxθ-/- muscle compared with mdx muscle, during the progression of the disease. Moreover, the expression level of Pax7 and Notch1, the pivotal regulators of SCs self-renewal, were upregulated in SCs isolated from mdxθ-/- muscle compared with mdx derived SCs. Likewise, the expression of the Notch ligands Delta1 and Jagged1 was higher in mdxθ-/- muscle compared with mdx. The expression level of Delta1 and Jagged1 was also higher in PKCθ-/- muscle compared with WT muscle following acute injury. In addition, lack of PKCθ prolonged the survival and sustained the differentiation of transplanted myogenic progenitors. Overall, our results suggest that lack of PKCθ promotes muscle repair in dystrophic mice, supporting stem cells survival and maintenance through increased Delta-Notch signaling. SN - 1422-0067 UR - https://www.unboundmedicine.com/medline/citation/32023816/Lack_of_PKCθ_Promotes_Regenerative_Ability_of_Muscle_Stem_Cells_in_Chronic_Muscle_Injury_ L2 - https://www.mdpi.com/resolver?pii=ijms21030932 DB - PRIME DP - Unbound Medicine ER -