Mesenchymal stem cells-derived HIF-1α-overexpressed extracellular vesicles ameliorate hypoxia-induced pancreatic β cell apoptosis and senescence through activating YTHDF1-mediated protective autophagy

Fang, Jiali; Chen, Zheng; Lai, Xingqiang; Yin, Wei; Guo, Yuhe; Zhang, Weiting; Ma, Junjie; Li, Guanghui; Zhang, Lei

doi:10.1016/j.bioorg.2022.106194

Cited by 13 publications

(9 citation statements)

References 44 publications

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“…Conversely, we found that Igfbp3 expression decreased when Hif1a was knocked down, regardless of the sugar type used. The induction of Hif1a influence the production of cytokines associated with the senescence-related phenotype 33,56 , aligning with our findings that demonstrate an increase in P16 and P21 immunosignals. Interestingly, we showed that IL4, IL8, and IL10 were increased in the fructose containing medium along with the reduction in GDF15, a growth factor that supports proliferation 26 .…”

Section: Discussionsupporting

confidence: 91%

“…For instance, high levels of glucose or fructose 32 as well as pollutants have the potential to induce stress factors like Hif1α, even under normoxic conditions, ultimately leading to senescence 31,32 . Notably, one of the significant challenges in stem cell transplantation is cell death induced by Hif1α activation 33 . Accordingly, we investigated transcript levels of Igfbp3 as a direct indicator of Hif1α activation 34,35 , as a consequence of fructose as the sole carbon source.…”

Section: Resultsmentioning

confidence: 99%

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Fructose vs. Glucose: Modulating Stem Cell Growth and Function Through Sugar Supplementation

Elsaid,

Wu,

Tee

2024

Preprint

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In multicellular organisms, stem cells are impacted by microenvironmental resources such as nutrient availability and oxygen tension for their survival, growth, and differentiation. However, the accessibility of these resources in the pericellular environment greatly varies from organ to organ. This divergence in resource availability leads to variations in the potency and differentiation potential of stem cells. Moreover, hexose and oxygen levels modulate cytokine production which is crucial for cell-cell communication as well as growth, and differentiation of stem cell. Hence, this study aims to explore the distinct effects of glucose and fructose, as well as different oxygen tensions, on the growth dynamics, cytokine production, and differentiation of stem cells.

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Section: Discussionsupporting

confidence: 91%

Section: Resultsmentioning

confidence: 99%

Fructose vs. Glucose: Modulating Stem Cell Growth and Function Through Sugar Supplementation

Elsaid,

Wu,

Tee

2024

Preprint

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“…HIF‐1α is the main regulatory factor under hypoxic conditions. In hypoxia‐induced cell stress models, HIF‐1α promotes the transcription of YTHDF1 and increases target protein levels by recognizing m6A‐methylated ATG2A, ATG14, and ATG5 and promoting their translation (Fang, Chen, et al, 2022; Li, Ni, et al, 2021). In NPC, ATG5 and ATG14 promote autophagy by increasing LC3‐II and reducing p62 (Ito et al, 2021; Wu et al, 2022), while knocking out the genes resulted in increased expression of Caspase3, Caspase9, and P16 proteins, indicating that ATG5 and ATG14 play a role in reducing NPC senescence and apoptosis under nutrition stress environments (Figure 4).…”

Section: M6a Methylation and Ivd Degenerationmentioning

confidence: 99%

M6A methylation‐regulated autophagy may be a new therapeutic target for intervertebral disc degeneration

Tao,

Yu,

et al. 2024

Cell Biology International

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Degeneration of intervertebral discs is considered one of the most important causes of low back pain and disability. The intervertebral disc (IVD) is characterized by its susceptibility to various stressors that accelerate the senescence and apoptosis of nucleus pulposus cells, resulting in the loss of these cells and dysfunction of the intervertebral disc. Therefore, how to reduce the loss of nucleus pulposus cells under stress environment is the main problem in treating intervertebral disc degeneration. Autophagy is a kind of programmed cell death, which can provide energy by recycling substances in cells. It is considered to be an effective method to reduce the senescence and apoptosis of nucleus pulposus cells under stress. However, further research is needed on the mechanisms by which autophagy of nucleus pulposus cells is regulated under stress environments. M6A methylation, as the most extensive RNA modification in eukaryotic cells, participates in various cellular biological functions and is believed to be related to the regulation of autophagy under stress environments, may play a significant role in nucleus pulposus responding to stress. This article first summarizes the effects of various stressors on the death and autophagy of nucleus pulposus cells. Then, it summarizes the regulatory mechanism of m6A methylation on autophagy‐related genes under stress and the role of these autophagy genes in nucleus pulposus cells. Finally, it proposes that the methylation modification of autophagy‐related genes regulated by m6A may become a new treatment approach for intervertebral disc degeneration, providing new insights and ideas for the clinical treatment of intervertebral disc degeneration.

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“…Notably, a similar protective mechanism was observed in pancreatic islet β-cells. Hypoxia-inducible factor 1-alpha upregulated ATG5, ATG2A, and ATG14 in a YTHDF1-dependent manner, triggering protective autophagy and ameliorating hypoxia-induced cytotoxicity ( Fang et al, 2022 ). Therefore, m 6 A aggravates metabolic syndromes by slowing down autophagy and cell damage in metabolic-related diseases by initiating cytoprotective autophagy mechanisms.…”

Section: M 6 a Regulates Metabolic Syndromes Throu...mentioning

confidence: 99%

The regulatory role of m6A methylation modification in metabolic syndrome pathogenesis and progression

Ye,

Zhang,

Zhang

et al. 2024

Front. Physiol.

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Metabolic syndromes are characterized by various complications caused by disrupted glucose and lipid metabolism, which are major factors affecting the health of a population. However, existing diagnostic and treatment strategies have limitations, such as the lack of early diagnostic and therapeutic approaches, variability in patient responses to treatment, and cost-effectiveness. Therefore, developing alternative solutions for metabolic syndromes is crucial. N6-methyladenosine (m6A) is one of the most abundant modifications that determine the fate of RNA. m6A modifications are closely associated with metabolic syndrome development and present novel prospects for clinical applications. Aberrant m6A modifications have been detected during inflammatory infiltration, apoptosis, autophagy, iron sagging, necrosis, and scorching during metabolic syndrome pathogenesis and progression. However, few reviews have systematically described the correlation between m6A modifications and these factors concerning metabolic syndrome pathogenesis and progression. This study summarizes the m6A methylation regulators and their roles in metabolic syndrome development, highlighting the potential of m6A modification as a biomarker in metabolic disorders.

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Mesenchymal stem cells-derived HIF-1α-overexpressed extracellular vesicles ameliorate hypoxia-induced pancreatic β cell apoptosis and senescence through activating YTHDF1-mediated protective autophagy

Cited by 13 publications

References 44 publications

Fructose vs. Glucose: Modulating Stem Cell Growth and Function Through Sugar Supplementation

Fructose vs. Glucose: Modulating Stem Cell Growth and Function Through Sugar Supplementation

M6A methylation‐regulated autophagy may be a new therapeutic target for intervertebral disc degeneration

The regulatory role of m6A methylation modification in metabolic syndrome pathogenesis and progression

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