Related Experiment Video
Updated: Apr 28, 2026
Author Spotlight: Isolation of Long Muscle Fibers from Mouse Hindlimb Muscles for Studying Excitation-Contraction Coupling Across Fiber Types
Published on: December 1, 2023
Intracellular MMP-2 activity in skeletal muscle is associated with type II fibers
Elin Hadler-Olsen1, Ann Iren Solli, Anne Hafstad
1Department of Medical Biology, Faculty of Health Sciences, University of Tromsø, Tromsø, Norway.
Abstract:
Matrix metalloproteinase 2 (MMP-2) is a proteolytic enzyme implicated in motility, differentiation, and regeneration of skeletal muscle fibers through processing of extracellular substrates. Although MMP-2 has been found to be localized intracellularly in cardiomyocytes where the enzyme is thought to contribute to post-ischemic loss of contractility, little is known about intracellular MMP-2 activity in skeletal muscle fibers. In the present study we demonstrate intracellular MMP-2 in normal skeletal muscle by immunohistochemical staining. Immunogold electron microscopic analyses indicated that the enzyme was concentrated in Z-lines of the sarcomers, in the nuclear membrane, and in mitochondria. By use of in situ zymography, we found that gelatinolytic activity in muscle fibers was co-localized with immunofluorecent staining for MMP-2. Staining for MMP-9, the other member of the gelatinase group of the MMPs, was negative. The broad-spectrum metalloprotease inhibitor EDTA and the selective gelatinase inhibitor CTT2, but not the cysteine inhibitor E64, strongly reduced the gelatinolytic activity. The intracellular gelatinolytic activity was much more prominent in fast twitch type II fibers than in slow twitch type I fibers, and there was a decrease in intracellular gelatinolytic activity and MMP-2 expression in muscles from mice exposed to high intensity interval training. Together our results indicate that MMP-2 is part of the intracellular proteolytic network in normal skeletal muscle, especially in fast twitch type II fibers. Further, the results suggest that intracellular MMP-2 in skeletal muscle fibers is active during normal homeostasis, and affected by the level of physical activity.
Insights
Matrix metalloproteinase 2 (MMP-2) is an intracellular enzyme found in skeletal muscle fibers, particularly in fast-twitch type II fibers. Its activity is linked to muscle homeostasis and is influenced by physical activity levels.
Area of Science:
- Biochemistry
- Molecular Biology
- Skeletal Muscle Physiology
Background:
- Matrix metalloproteinase 2 (MMP-2) is a proteolytic enzyme involved in extracellular matrix remodeling.
- While intracellular MMP-2 is known in cardiomyocytes, its role in skeletal muscle fibers remains largely uncharacterized.
- Skeletal muscle regeneration and motility are processes potentially influenced by MMP-2 activity.
Purpose of the Study:
- To investigate the presence and activity of intracellular MMP-2 in normal skeletal muscle fibers.
- To determine the subcellular localization of MMP-2 within skeletal muscle.
- To assess the impact of physical activity on intracellular MMP-2 activity and expression.
Main Methods:
- Immunohistochemical staining to detect MMP-2 localization in skeletal muscle.
- Immunogold electron microscopy for high-resolution subcellular localization.
- In situ zymography to assess gelatinolytic activity.
- Inhibition studies using EDTA, CTT2, and E64 to characterize the activity.
- Comparison of activity between fast-twitch (type II) and slow-twitch (type I) fibers.
- Analysis of MMP-2 expression and activity in response to high-intensity interval training.
Main Results:
- Intracellular MMP-2 was detected in normal skeletal muscle fibers, concentrated in Z-lines, nuclear membrane, and mitochondria.
- Gelatinolytic activity, indicative of MMP-2 activity, was co-localized with MMP-2 staining.
- MMP-9 was not detected.
- Intracellular gelatinolytic activity was significantly higher in fast-twitch type II fibers compared to slow-twitch type I fibers.
- High-intensity interval training led to decreased intracellular gelatinolytic activity and MMP-2 expression.
Conclusions:
- MMP-2 is an active component of the intracellular proteolytic network in skeletal muscle, particularly in fast-twitch fibers.
- Intracellular MMP-2 activity in skeletal muscle is present during normal homeostasis.
- Physical activity levels modulate intracellular MMP-2 activity and expression in skeletal muscle fibers.
Related Concept Videos
01:23Role of Matrix Metalloproteases in Degradation of ECM
01:13Microscopic Anatomy of Skeletal Muscles
The muscle sarcolemma is a plasma membrane enclosing each muscle cell that conducts electrical signals called action potentials. The sarcolemma extends into the cell to form T-tubules, ensuring the neural impulses are uniformly distributed across the entire muscle...
01:26Cross-bridge Cycle
01:21Satellite Stem Cells and Muscular Dystrophy
01:16Actin and Myosin in Muscle Contraction
01:25Smooth Muscle Contraction
The onset of contraction is triggered by an increase in calcium ions within the sarcoplasm, similar to the process in striated muscle. However, smooth muscles have a relatively smaller reservoir of the sarcoplasmic...