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Updated: Jan 1, 2026
Immunolabelling Myofiber Degeneration in Muscle Biopsies
Published on: December 5, 2019
Muscle death participates in myofibrillar abnormalities in FHL1 knockout mice
Jingjing Ding1, Yanfei Cong1, Fang Li1
1Medical Research Center of Shengjing Hospital, China Medical University, Shenyang, 110004, China; Key Laboratory of Research and Application of Animal Model for Environmental and Metabolic Diseases, Liaoning Province, China.
Background:
Mutations in the four and-a-half LIM domain protein 1 (FHL1) gene or FHL1 protein deletion have been identified as the cause of rare hereditary myopathies or cardiomyopathies. In our previous study, autophagy activation was associated with myofibrillar abnormalities in FHL1 knockout (KO) mice. P2RX7 induces cell death, such as autophagy, pyroptosis or apoptosis via cell-specific downstream signaling; however, the roles of P2RX7 in pyroptosis or apoptosis in myofibrillar abnormalities in FHL1 KO mice have not been well elucidated.
Methods:
In this study, skeletal muscle and heart of 2.5 months old WT and FHL1 KO male mice histomorphology were examined by hematoxylin and eosin staining. The indicators for pyroptosis (NLRP3; ASC; cleaved-caspase1; IL-1β), apoptosis (Apaf-1; Bcl-2; caspase9; cleaved-caspase3), and P2RX7 were detected in the triceps (Tri), tibialis anterior muscles (TA), and heart by western blot and/or immunohistochemistry in WT and FHL1 KO male mice.
Results:
Indicators for pyroptosis (ASC; cleaved-caspase1; IL-1β) and apoptosis (Apaf-1 and cleaved-caspase3), as well as P2RX7 were upregulated in Tri, tibialis TA, and heart in FHL1 KO mice, indicating pyroptosis and apoptosis play important roles in myofibrillar abnormalities in FHL1 KO mice.
Conclusions:
P2RX7 may participate in myofibrillar abnormalities by activating pyroptosis and apoptosis in FHL1 KO mice. These findings have basic implications for the understanding of myopathies induced by FHL1 deficiency and provide new avenues for the treatment of these hereditary myopathies by modulating P2RX7.
Insights
The purinergic receptor P2RX7 may drive myofibrillar abnormalities in FHL1 deficiency myopathies by triggering pyroptosis and apoptosis. Targeting P2RX7 offers a potential therapeutic strategy for these rare hereditary muscle diseases.
Area of Science:
- Muscle physiology and pathology
- Cell death pathways
- Molecular genetics
Background:
- Mutations in the four and-a-half LIM domain protein 1 (FHL1) gene cause hereditary myopathies and cardiomyopathies.
- Autophagy activation was previously linked to myofibrillar abnormalities in FHL1 knockout (KO) mice.
- The role of P2RX7 in pyroptosis or apoptosis in FHL1-deficient myopathies remains unclear.
Purpose of the Study:
- To investigate the involvement of P2RX7 in pyroptosis and apoptosis in FHL1 KO mice.
- To elucidate the mechanisms underlying myofibrillar abnormalities in FHL1 deficiency.
Main Methods:
- Histomorphology of skeletal muscle and heart from WT and FHL1 KO mice was assessed.
- Western blot and immunohistochemistry were used to detect indicators of pyroptosis, apoptosis, and P2RX7 expression.
- Specific tissues examined included triceps, tibialis anterior, and heart.
Main Results:
- Upregulation of pyroptosis indicators (ASC, cleaved-caspase1, IL-1β) and apoptosis indicators (Apaf-1, cleaved-caspase3) was observed in FHL1 KO mice.
- P2RX7 was also upregulated in the muscles and heart of FHL1 KO mice.
- These findings suggest pyroptosis and apoptosis are key contributors to myofibrillar abnormalities.
Conclusions:
- P2RX7 may contribute to myofibrillar abnormalities by activating pyroptosis and apoptosis in FHL1 KO mice.
- These results enhance understanding of FHL1 deficiency-induced myopathies.
- Modulating P2RX7 presents a potential therapeutic approach for hereditary myopathies.
