Jiale Tan, Yuqi Li, Jie Zhang, Beijie Qi, Jiwu Chen, Yaying Sun
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引用次数: 0
Abstract
Muscle fatty infiltration (MFI) was characterized by the pathological accumulation of fat within skeletal muscle tissue. Previous studies have found that the progress of this pathological phenomenon in aging, acute muscle injury, and other conditions was triggered by the activation and adipogenic differentiation of the key cell population, fibro/adipogenic progenitors (FAPs), but there were few studies on the fat infiltration caused by disused skeletal muscle atrophy, and the regulatory role of FAPs in this situation has not been deeply explored, leaving the related molecular mechanisms still unknown. In this study, we conducted single-cell RNA sequencing on the disused skeletal muscle. The aberrant proliferation of FAPs in this state was found by subsequent analysis, along with the high expression of the ferroptosis inhibitory gene in the activated FAPs. By immunofluorescence staining, we verified the proliferation and adipogenic differentiation of FAPs, which proved the role of FAPs in fat infiltration of disused skeletal muscle. In order to further verify the relationship between ferroptosis inhibition and FAPs activation/adipogenic differentiation, we used ferrostatin-1, a commonly used ferroptosis inhibitor, to treat skeletal muscle fibroblasts and FAPs in vitro, and verified the enhancement of ferroptosis inhibition on their adipogenic/fibrogenic ability. Our study pinpointed the effect of aberrant activation of FAPs on MFI in disused skeletal muscle, and preliminarily recognized the potential effect of ferroptosis on the adipogenic differentiation of FAPs. KEY MESSAGES: • Muscle fatty infiltration (MFI) was characterized by the pathological accumulation of fat within skeletal muscle. Fibro/adipogenic progenitors (FAPs) were thought to be crucial regulators of MFI, but their correlations in disused skeletal muscle were unspecified. • In this study, we conducted single-cell RNA sequencing on the disused skeletal muscle and recognized the aberrant proliferation of FAPs along with the upregulated ferroptosis inhibition genes in this status. • Subsequently, we used ferrostatin-1 (ferroptosis inhibitor) to treat skeletal muscle fibroblasts in vitro, and verified the enhancement of ferroptosis inhibition on their adipogenic/fibrogenic ability. • Our study pinpointed the effect of aberrant activation of FAPs on MFI in disused skeletal muscle, and preliminarily recognized the potential effect of ferroptosis on the adipogenic differentiation of FAPs.
期刊介绍:
The Journal of Molecular Medicine publishes original research articles and review articles that range from basic findings in mechanisms of disease pathogenesis to therapy. The focus includes all human diseases, including but not limited to:
Aging, angiogenesis, autoimmune diseases as well as other inflammatory diseases, cancer, cardiovascular diseases, development and differentiation, endocrinology, gastrointestinal diseases and hepatology, genetics and epigenetics, hematology, hypoxia research, immunology, infectious diseases, metabolic disorders, neuroscience of diseases, -omics based disease research, regenerative medicine, and stem cell research.
Studies solely based on cell lines will not be considered. Studies that are based on model organisms will be considered as long as they are directly relevant to human disease.