Abstract
Statins are the most effective therapeutic agents for reducing cholesterol synthesis. Given their widespread use, many adverse effects from statins have been reported; of these, musculoskeletal complications occurred in 15% of patients after receiving statins for 6 months, and simvastatin was the most commonly administered statin among these cases. This study investigated the negative effects of simvastatin on skeletal muscle cells. We performed RNA sequencing analysis to determine gene expression in simvastatin-treated cells. Cell proliferation and migration were examined through cell cycle analysis and the transwell filter migration assay, respectively. Cytoskeleton rearrangement was examined through F-actin and tubulin staining. Western blot analysis was performed to determine the expression of cell cycle-regulated and cytoskeleton-related proteins. Transfection of small interfering RNAs (siRNAs) was performed to validate the role of cofilin and stathmin in the simvastatin-mediated inhibition of cell migration. The results revealed that simvastatin inhibited the proliferation and migration of skeletal muscle cells and affected the rearrangement of F-actin and tubulin. Simvastatin reduced the expression of cofilin and stathmin. The knockdown of both cofilin and stathmin by specific siRNA synergistically impaired cell migration. In conclusion, our results indicated that simvastatin inhibited skeletal muscle cell migration by reducing the expressions of cofilin and stathmin.
Highlights
The results of Gene ontology (GO)enrichment analysis revealed that differentially expressed genes (DEGs) downregulated by simvastatin were related to nuclear division, DNA replication, and microtubule cytoskeleton organization (Figure 1)
The results indicated that simvastatin inhibited the expression of genes related to cell proliferation and migration
Simvastatin Inhibited the Spreading of Skeletal Muscle Cells
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Neutrophils and macrophages invade the injured site from 12 h to 4 days after injury These inflammatory cells remove necrotic muscle cells through phagocytosis and release growth factors and cytokines, including insulin-like growth factor 1, transforming growth factor-β, interferon-γ, and tumor necrosis factor. Cell proliferation plays a key role in the healing process of injured muscle. Similar to other types of cells, the cell division cycle of skeletal muscle cells has four stages: gap 1 (G1), synthesis (S), gap 2 (G2), and mitosis (M) This tightly controlled temporal order is controlled by the sequential activation of various protein kinases known as cyclin-dependent kinases (CDKs) that form a complex with various cyclins [14]. The cytoskeleton, which includes actin microfilaments, microtubules, and intermediate filaments, plays a crucial role in the cell migration process. This study investigated the effects of simvastatin on the migratory ability of skeletal muscle cells and the underlying molecular mechanism
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