Abstract
Myopathic processes affect skeletal muscle and heart. In the muscular dystrophies, which are a subset of myopathies, muscle cells are gradually replaced by fibrosis and fat, impairing muscle function as well as regeneration and repair. In addition to skeletal muscle, these genetic disorders often also affect the heart, where fibrofatty infiltration progressively accumulates in the myocardium, impairing heart function. Although considerable effort has focused on gene-corrective and gene-replacement approaches to stabilize myofibers and cardiomyocytes, the continual and ongoing deposition of extracellular matrix itself contributes to tissue and organ dysfunction. Transcriptomic and proteomic profiling, along with high-resolution imaging and biophysical measurements, have been applied to define extracellular matrix components and their role in contributing to cardiac and skeletal muscle weakness. More recently, decellularization methods have been adapted to an on-slide format to preserve the spatial geography of the extracellular matrix, allowing new insight into matrix remodeling and its direct role in suppressing regeneration in muscle. This review highlights recent literature with focus on the extracellular matrix and molecular mechanisms that contribute to muscle and heart fibrotic disorders. We will also compare how the myopathic matrix differs from healthy matrix, emphasizing how the pathological matrix contributes to disease.
Original language | English (US) |
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Pages (from-to) | C1244-C1251 |
Journal | American Journal of Physiology - Cell Physiology |
Volume | 325 |
Issue number | 5 |
DOIs | |
State | Published - Nov 2023 |
Funding
This study is supported by the NIH Grants AR052646, HL061322, HL167813, NS047726, NS127383, and T32HL134633.
Keywords
- acellular myoscaffolds
- decellularization
- fibrosis
- heart
- muscle
ASJC Scopus subject areas
- Physiology
- Cell Biology