Multi-Cellular Functions of MG53 in Muscle Calcium Signaling and Regeneration

Benissan-Messan, Dathe; Zhu, Hua; Zhong, Weina; Tan, Tao; Ma, Jianjie; Lee, Peter H.U.

doi:10.3389/fphys.2020.583393

Cited by 10 publications

(9 citation statements)

References 80 publications

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“…It may be anticipated that, similar to the liver, other organs could also release proteins capable of modifying insulin receptor activation, finally leading to changes in metabolic performance. A potential candidate is mitsugumin 53 (MG53), a muscle-specific protein with multiple functions including muscle regeneration, calcium homeostasis, excitationcontraction coupling, and myogenesis [26]. In 2013, it was reported that MG53 is upregulated in models of insulin resistance and that it modifies insulin signaling by targeting the degradation of the insulin receptor β-subunit and of IRS1 by its ubiquitin E3 ligase activity [27].…”

Section: Inhibitory Modulatorsmentioning

confidence: 99%

“…In 2013, it was reported that MG53 is upregulated in models of insulin resistance and that it modifies insulin signaling by targeting the degradation of the insulin receptor β-subunit and of IRS1 by its ubiquitin E3 ligase activity [27]. Recently, the same group reported that MG53 is a myokine/cardiokine secreted from striated muscles in response to high glucose or insulin in both rodents and humans [26]. Further, the serum level of MG53 is upregulated in obesity and T2DM, and administration of MG53 was found to inhibit the insulin response in multiple organs.…”

Section: Inhibitory Modulatorsmentioning

confidence: 99%

“…These findings define circulating MG53 as a potential target for treating insulin resistance and T2DM. However, the role of MG53 in diabetes has remained highly controversial [26]. Thus, transgenic mice with sustained overexpression of MG53 exhibit an unaltered metabolic function and improved tissue repair capacity [29].…”

Section: Inhibitory Modulatorsmentioning

confidence: 99%

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Organ Crosstalk and the Modulation of Insulin Signaling

Romero

Eckel

2021

Cells

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A highly complex network of organ communication plays a key role in regulating metabolic homeostasis, specifically due to the modulation of the insulin signaling machinery. As a paradigm, the role of adipose tissue in organ crosstalk has been extensively investigated, but tissues such as muscles and the liver are equally important players in this scenario. Perturbation of organ crosstalk is a hallmark of insulin resistance, emphasizing the importance of crosstalk molecules in the modulation of insulin signaling, potentially leading to defects in insulin action. Classically secreted proteins are major crosstalk molecules and are able to affect insulin signaling in both directions. In this review, we aim to focus on some crosstalk mediators with an impact on the early steps of insulin signaling. In addition, we also summarize the current knowledge on the role of extracellular vesicles in relation to insulin signaling, a more recently discovered additional component of organ crosstalk. Finally, an attempt will be made to identify inter-connections between these two pathways of organ crosstalk and the potential impact on the insulin signaling network.

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Section: Inhibitory Modulatorsmentioning

confidence: 99%

Section: Inhibitory Modulatorsmentioning

confidence: 99%

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Organ Crosstalk and the Modulation of Insulin Signaling

Romero

Eckel

2021

Cells

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“…TRIM72, which remarkably expressed in skeletal and heart muscles, is a protein implicated in membrane repairment [ 22 , 23 ]. Considering that DMD disease manifests as membrane impairment, we explored how TRIM72 expressed in mdx mice.…”

Section: Resultsmentioning

confidence: 99%

TRIM72 Alleviates Muscle Inflammation in mdx Mice via Promoting Mitophagy-Mediated NLRP3 Inflammasome Inactivation

et al. 2023

Oxidative Medicine and Cellular Longevity

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Chronic muscle inflammation exacerbates the pathogenesis of Duchenne muscular dystrophy (DMD), which is characterized by progressive muscle degeneration and weakness. NLRP3 (nucleotide-binding domain and leucine-rich repeat pyrin domain containing 3) inflammasome plays a key role in the inflammatory process, and its abnormal activation leads to a variety of inflammatory or immune diseases. TRIM72 (MG53) is a protective myokine for tissue repair and regeneration. However, little is known about the potential impact of TRIM72 in the crosstalk between mitophagy and inflammatory process of DMD. Here, 10-week-old male mdx mice were injected intramuscularly with adeno-associated virus (AAV-TRIM72) to overexpress TRIM72 protein for 6 weeks. Then, skeletal muscle samples were collected, and relevant parameters were measured by histopathological analysis and molecular biology techniques. C2C12 cell line was transfected with lentivirus (LV-TRIM72) to overexpress or siRNA (si-TRIM72) to suppress the TRIM72 expression for the following experiment. Our data firstly showed that the TRIM72 expression was decreased in skeletal muscles of mdx mice. Then, we observed the increased NLRP3 inflammasome and impaired mitophagy in mdx mice compared with wild type mice. In mdx mice, administration of AAV-TRIM72 alleviated the accumulation of NLRP3 inflammasome and the consequent IL-18 and IL1β maturation by inducing autophagy, while this protective effect was reversed by chloroquine. Mitochondrial reactive oxygen species (mtROS), as a recognized activator for NLRP3 inflammasome, was attenuated by TRIM72 through the induction of mitophagy in C2C12 cells. Additionally, we proposed that the TRIM72 overexpression might promote mitophagy through both the early stage by PI3K-AKT pathway and the late stage by autolysosome fusion. In conclusion, the current study suggests that TRIM72 prevents DMD inflammation via decreasing NLRP3 inflammasomes and enhancing mitophagy. Collectively, our study provides insight into TRIM72 as a promising target for therapeutic intervention for DMD.

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“… 28–30 Cardiac-specific transgenic expression of MG53 induces severe diabetic cardiomyopathy in mice, accompanied by insulin resistance, increased lipid accumulation, myocardial hypertrophy, fibrosis, and cardiac dysfunction, 31 whereas others claimed that it has therapeutic applications, such as protecting injured mitochondria and inducing muscle regeneration. 32 , 33 Mitophagy ubiquitin ligases appear to have complex functions, and a single ligase may not modulate every form of mitophagy, but the process of mitophagy and the formation of phagosomes are likely mediated and regulated by networks of these proteins.…”

Section: Pink1 and Parkinmentioning

confidence: 99%