Inhibition of MAT2A Impairs Skeletal Muscle Repair Function

Xiao, Wanli; Huang, Tian-E; Zhou, Jing; Wang, Benhui; Wang, Xiang; Zeng, Weirong; Wang, Qiquan; Lan, Xinqiang; Xiang, Yang

doi:10.3390/biom14091098

Open AccessArticle

Inhibition of MAT2A Impairs Skeletal Muscle Repair Function

by

Wanli Xiao

,

Tian-E Huang

,

Jing Zhou

,

Benhui Wang

,

Xiang Wang

,

Weirong Zeng

,

Qiquan Wang

,

Xinqiang Lan

and

Yang Xiang

^*

Metabolic Control and Aging—Jiangxi Key Laboratory of Aging and Diseases, Human Aging Research Institute (HARI), School of Life Science, Nanchang University, Nanchang 330031, China

^*

Author to whom correspondence should be addressed.

Biomolecules 2024, 14(9), 1098; https://doi.org/10.3390/biom14091098

Submission received: 8 July 2024 / Revised: 5 August 2024 / Accepted: 6 August 2024 / Published: 2 September 2024

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Abstract

The regenerative capacity of muscle, which primarily relies on anabolic processes, diminishes with age, thereby reducing the effectiveness of therapeutic interventions aimed at treating age-related muscle atrophy. In this study, we observed a decline in the expression of methionine adenosine transferase 2A (MAT2A), which synthesizes S-adenosylmethionine (SAM), in the muscle tissues of both aged humans and mice. Considering MAT2A’s critical role in anabolism, we hypothesized that its reduced expression contributes to the impaired regenerative capacity of aging skeletal muscle. Mimicking this age-related reduction in the MAT2A level, either by reducing gene expression or inhibiting enzymatic activity, led to inhibiting their differentiation into myotubes. In vivo, inhibiting MAT2A activity aggravated BaCl₂-induced skeletal muscle damage and decreased the number of satellite cells, whereas supplementation with SAM improved these effects. RNA-sequencing analysis further revealed that the Fas cell surface death receptor (Fas) gene was upregulated in Mat2a-knockdown C2C12 cells. Suppressing MAT2A expression or activity elevated Fas protein levels and increased the proportion of apoptotic cells. Additionally, inhibition of MAT2A expression or activity increased p53 expression. In conclusion, our findings demonstrated that impaired MAT2A expression or activity compromised the regeneration and repair capabilities of skeletal muscle, partially through p53–Fas-mediated apoptosis.

Keywords: Mat2a; C2C12; skeletal muscle; Fas; regeneration

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MDPI and ACS Style

Xiao, W.; Huang, T.-E.; Zhou, J.; Wang, B.; Wang, X.; Zeng, W.; Wang, Q.; Lan, X.; Xiang, Y. Inhibition of MAT2A Impairs Skeletal Muscle Repair Function. Biomolecules 2024, 14, 1098. https://doi.org/10.3390/biom14091098

AMA Style

Xiao W, Huang T-E, Zhou J, Wang B, Wang X, Zeng W, Wang Q, Lan X, Xiang Y. Inhibition of MAT2A Impairs Skeletal Muscle Repair Function. Biomolecules. 2024; 14(9):1098. https://doi.org/10.3390/biom14091098

Chicago/Turabian Style

Xiao, Wanli, Tian-E Huang, Jing Zhou, Benhui Wang, Xiang Wang, Weirong Zeng, Qiquan Wang, Xinqiang Lan, and Yang Xiang. 2024. "Inhibition of MAT2A Impairs Skeletal Muscle Repair Function" Biomolecules 14, no. 9: 1098. https://doi.org/10.3390/biom14091098

APA Style

Xiao, W., Huang, T.-E., Zhou, J., Wang, B., Wang, X., Zeng, W., Wang, Q., Lan, X., & Xiang, Y. (2024). Inhibition of MAT2A Impairs Skeletal Muscle Repair Function. Biomolecules, 14(9), 1098. https://doi.org/10.3390/biom14091098

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Inhibition of MAT2A Impairs Skeletal Muscle Repair Function

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