Sirt2 positively regulates muscle regeneration after Notexin-induced muscle injury
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Updated: Sep 21, 2025
Analyzing Satellite Cell Function During Skeletal Muscle Regeneration by Cardiotoxin Injury and Injection of Self-delivering siRNA In Vivo
Published on: September 18, 2019
Eun-Joo Lee1, Myeong-Mi Lee1, SunYoung Park1
1College of Veterinary Medicine, Department of Veterinary Pathology, Kyungpook National University, 41566, Daegu City, Republic of Korea.
Abstract:
Sirt2 regulates various biological processes by deacetylating target genes. Despite roles in regulating proliferation, cell cycle, and glucose metabolism, which are closely associated with skeletal muscle physiology, Sirt2 functions in this tissue remain unclear. In this study, genetic deletion of Sirt2 delayed muscle regeneration after Notexin-induced muscle injury. Gene expressions of myogenic regulatory factors, including Myf5, MyoD, and Myogenin, and cell cycle regulators, such as cyclin D1 and CDK2, were repressed in Sirt2 knockout mice after injury. Also, Sirt2 knockout mice presented muscle atrophy after muscle injury which is associated with the down-regulation of anabolic signaling and the up-regulation of catabolic signaling, in particular, increased atrogin1 transcriptional expression. Thus, Sirt2 positively regulated skeletal muscle regeneration after muscle injury by regulating transcriptional expression involved in myogenesis, cell cycle, and anabolic and catabolic signaling. Based on the in vivo analyses, Sirt2 could function as an interventional therapeutic for chronic myopathy, which is characterized by impaired muscle regeneration and muscle atrophy.
Insights
Sirt2 protein is crucial for skeletal muscle regeneration. Its absence delays recovery and causes muscle atrophy by affecting key gene expressions involved in muscle repair and growth.
Area of Science:
- Skeletal muscle physiology
- Molecular biology
- Biochemistry
Background:
- Sirtuin 2 (Sirt2) regulates biological processes via deacetylation.
- Sirt2's role in skeletal muscle physiology, including proliferation and cell cycle, is not well understood.
- Understanding Sirt2's function is vital for addressing muscle disorders.
Purpose of the Study:
- To investigate the function of Sirt2 in skeletal muscle regeneration after injury.
- To elucidate the molecular mechanisms underlying Sirt2's role in myogenesis and muscle atrophy.
Main Methods:
- Utilized a mouse model with genetic deletion of Sirt2 (Sirt2 knockout).
- Induced skeletal muscle injury using Notexin.
- Analyzed gene expression of myogenic regulatory factors (Myf5, MyoD, Myogenin) and cell cycle regulators (cyclin D1, CDK2).
- Assessed anabolic and catabolic signaling pathways, including atrogin1 expression.
Main Results:
- Genetic deletion of Sirt2 significantly delayed muscle regeneration post-injury.
- Sirt2 knockout mice exhibited repressed expression of key myogenic and cell cycle regulatory genes.
- Muscle atrophy was observed in Sirt2 knockout mice, linked to altered anabolic and catabolic signaling, notably increased atrogin1 expression.
Conclusions:
- Sirt2 positively regulates skeletal muscle regeneration by controlling gene expression in myogenesis, cell cycle, and signaling pathways.
- Sirt2 plays a critical role in preventing muscle atrophy following injury.
- Sirt2 represents a potential therapeutic target for chronic myopathies characterized by impaired regeneration and atrophy.
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