VEGFA Promotes Skeletal Muscle Regeneration in Aging

Endo, Yori; Hwang, Charles; Zhang, Yuteng; Olumi, Shayan; Koh, Daniel J; Zhu, Christina; Neppl, Ronald L.; Agarwal, Shailesh; Sinha, Indranil

doi:10.1002/adbi.202200320

Cited by 5 publications

(3 citation statements)

References 51 publications

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“…demonstrated that restoration of aging‐related decline in muscle VEGF levels with ML228 could improve regenerative response in aged muscle and reduce fibrofatty infiltration. [ 65 ] The exact mechanism underlying this is yet to be elucidated; however, it is noteworthy that the restoration of HIF signaling lost with aging in skeletal muscle improves its overall regenerative response, in agreement with the known effects of HIFs in satellite cells and myoblasts. ML228 or pharmacological targeting of HIF in aged muscle therefore presents an attractive method for restoring its regenerative capacity.…”

Section: Muscle Regenerationmentioning

confidence: 53%

The Role of Hypoxia and Hypoxia Signaling in Skeletal Muscle Physiology

Endo,

Zhu,

Giunta

et al. 2023

Advanced Biology

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Hypoxia and hypoxia signaling play an integral role in regulating skeletal muscle physiology. Environmental hypoxia and tissue hypoxia in muscles cue for their appropriate physiological response and adaptation, and cause an array of cellular and metabolic changes. In addition, muscle stem cells (satellite cells), exist in a hypoxic state, and this intrinsic hypoxic state correlates with their quiescence and stemness. The mechanisms of hypoxia‐mediated regulation of satellite cells and myogenesis are yet to be characterized, and their seemingly contradicting effects reported leave their exact roles somewhat perplexing. This review summarizes the recent findings on the effect of hypoxia and hypoxia signaling on the key aspects of muscle physiology, namely, stem cell maintenance and myogenesis with a particular attention given to distinguish the intrinsic versus local hypoxia in an attempt to better understand their respective regulatory roles and how their relationship affects the overall response. This review further describes their mechanistic links and their possible implications on the relevant pathologies and therapeutics.

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Section: Muscle Regenerationmentioning

confidence: 53%

The Role of Hypoxia and Hypoxia Signaling in Skeletal Muscle Physiology

Endo,

Zhu,

Giunta

et al. 2023

Advanced Biology

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“…DUX4-mediated VEGF disturbances are in accordance with corresponding HIF1α expression patterns during muscle cell differentiation. This mediator of angiogenesis is induced by hypoxic and ischemic conditions [ 68 , 69 ] through HIF1α [ 57 , 58 ] and contributes to myoblast differentiation [ 70 ] and skeletal muscle regeneration [ 71 , 72 , 73 , 74 ]. Even if VEGF was primarily studied here to assess HIF1α transcriptional activity, our results highlight an interest in further investigating the HIF1α–VEGF axis in FSHD, for which evidence of vascular troubles was reported.…”

Section: Discussionmentioning

confidence: 99%

The DUX4–HIF1α Axis in Murine and Human Muscle Cells: A Link More Complex Than Expected

Nguyen,

Limpens,

Bouhmidi

et al. 2024

IJMS

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FacioScapuloHumeral muscular Dystrophy (FSHD) is one of the most prevalent inherited muscle disorders and is linked to the inappropriate expression of the DUX4 transcription factor in skeletal muscles. The deregulated molecular network causing FSHD muscle dysfunction and pathology is not well understood. It has been shown that the hypoxia response factor HIF1α is critically disturbed in FSHD and has a major role in DUX4-induced cell death. In this study, we further explored the relationship between DUX4 and HIF1α. We found that the DUX4 and HIF1α link differed according to the stage of myogenic differentiation and was conserved between human and mouse muscle. Furthermore, we found that HIF1α knockdown in a mouse model of DUX4 local expression exacerbated DUX4-mediated muscle fibrosis. Our data indicate that the suggested role of HIF1α in DUX4 toxicity is complex and that targeting HIF1α might be challenging in the context of FSHD therapeutic approaches.

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“…Thus, more large-sample studies need to be conducted to further validate the relationship. VEGF was proven to be a protective factor in mice, can prevent age-related losses of capillaries, enhances the perfusion and function of organs, and extends life span ( 63 ). However, there were no studies on the potential role of VEGF on sarcopenia in humans.…”

Section: Discussionmentioning

confidence: 99%

The causal association between circulating cytokines with the risk of frailty and sarcopenia under the perspective of geroscience

Wang,

Wan

et al. 2024

Front. Endocrinol.

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IntroductionCirculating cytokines were considered to play a critical role in the initiation and propagation of sarcopenia and frailty from observational studies. This study aimed to find the casual association between circulating cytokines and sarcopenia and frailty from a genetic perspective by two-sample Mendelian randomization (MR) analysis.MethodsData for 41 circulating cytokines were extracted from the genome-wide association study dataset of 8,293 European participants. Inverse-variance weighted (IVW) method, MR-Egger, and weighted median method were applied to assess the relationship of circulating cytokines with the risk of aging-related syndromes and frailty. Furthermore, MR-Egger regression was used to indicate the directional pleiotropy, and Cochran’s Q test was used to verify the potential heterogeneity. The “leave-one-out” method was applied to visualize whether there was a causal relationship affected by only one anomalous single-nucleotide polymorphisms.ResultsGenetic predisposition to increasing levels of interleukin-10 (IL-10), IL-12, and vascular endothelial growth factor (VEGF) was associated with the higher risk of low hand grip strength according to the IVW method [R = 1.05, 95% CI = 1.01–1.10, P = 0.028, false discovery rate (FDR)–adjusted P = 1.000; OR = 1.03, 95% CI = 1.00–1.07, P = 0.042, FDR-adjusted P = 0.784; OR = 1.02, 95% CI = 1.00–1.05, P = 0.038, FDR-adjusted P = 0.567]. Furthermore, genetically determined higher macrophage colony-stimulating factors (M-CSFs) were associated with a lower presence of appendicular lean mass (OR = 1.01, 95% CI = 1.00–1.02, P = 0.003, FDR-adjusted P = 0.103). Monokine induced by interferon-γ (MIG) and tumor necrosis factor–beta (TNF-β) were associated with a higher risk of frailty (OR = 1.03, 95% CI = 1.01–1.05, P < 0.0001, FDR-adjusted P = 0.012; OR = 1.01, 95% CI = 1.00–1.03, P = 0.013, FDR-adjusted P = 0.259). In this study, we did not find heterogeneity and horizontal pleiotropy between the circulating cytokines and the risk of frailty and sarcopenia.ConclusionGenetic predisposition to assess IL-10, IL-12, and VEGF levels was associated with a higher risk of low hand grip strength and M-CSF with the presence of appendicular lean mass. The high levels of TNF-β and MIG were associated with a higher risk of frailty. More studies will be required to explore the molecular biological mechanisms underlying the action of inflammatory factors.

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VEGFA Promotes Skeletal Muscle Regeneration in Aging

Cited by 5 publications

References 51 publications

The Role of Hypoxia and Hypoxia Signaling in Skeletal Muscle Physiology

The Role of Hypoxia and Hypoxia Signaling in Skeletal Muscle Physiology

The DUX4–HIF1α Axis in Murine and Human Muscle Cells: A Link More Complex Than Expected

The causal association between circulating cytokines with the risk of frailty and sarcopenia under the perspective of geroscience

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