The whole profiling and competing endogenous RNA network analyses of noncoding RNAs in adipose-derived stem cells from diabetic, old, and young patients

Ren, Sen; Xiong, Hairong; Chen, Jing; Yang, Xiaofan; Liu, Yutian; Guo, Jiahe; Jiang, Tao; Zhao, Xu; Yuan, Meng; Liu, Yang; Zhou, Nan; Chen, Hongrui; Li, Wenqing; Machens, Hans‐Günther; Chen, Zhenbing

doi:10.1186/s13287-021-02388-5

Cited by 33 publications

(30 citation statements)

References 69 publications

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“…However, chrysin-treated diabetic BMSCs still exhibited significantly lower viability and poorer osteogenesis than the chrysin-treated normal BMSCs, which is possible due to DNA damage and senescence caused by diabetes. 28,30 The PI3K/AKT pathway plays a vital role in multiple physiological processes, including glucose uptake, glycolysis, lipid synthesis, nucleotide synthesis, and protein synthesis. 31 Due to its critical role in cell metabolism, the PI3K/AKT pathway is intricately linked to multiple diseases, including cardiovascular disease, diabetes, and cancer.…”

Section: Discussionmentioning

confidence: 99%

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Chrysin Attenuates High Glucose-Induced BMSC Dysfunction via the Activation of the PI3K/AKT/Nrf2 Signaling Pathway

Li¹,

Wang²

2022

DDDT

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Purpose: High glucose environment in diabetes mellitus induces the dysfunction of bone marrow-derived mesenchymal stromal cells (BMSCs) and impairs bone regeneration. Chrysin is a natural polyphenol with outstanding anti-inflammation and anti-oxidation ability. However, whether and how chrysin affects BMSCs in high glucose conditions remain poorly understood. The present study aimed to explore the effects and underlying mechanisms of chrysin on the BMSCs exposed to high glucose environment. Materials and Methods: Cell viability was detected by cell counting kit 8 assay and 5ethynyl-2'-deoxyuridine staining, while cell apoptosis was determined through flow cytometry using Annexin V-FITC/PI kit. The oxidative stress in BMSCs was evaluated by detecting the reactive oxygen species production, malondialdehyde content, and superoxide dismutase activity. Alkaline phosphatase staining, Alizarin Red staining, and quantitative real-time PCR were performed to determine the osteogenic differentiation. Western blot was used to examine the expression of the PI3K/ATK/Nrf2 signaling pathway. Furthermore, chrysin was injected into calvarial defects of type 1 diabetic SD rats to assess its in vivo bone formation capability. Results: Chrysin reduced oxidative stress, increased cell viability, and promoted osteogenic differentiation in BMSCs exposed to high glucose. Blocking PI3K/ATK/Nrf2 signaling pathway weakened the beneficial effects of chrysin, indicating that chrysin at least partly worked through the PI3K/ATK/Nrf2 pathway. Conclusion: Chrysin can protect BMSCs from high glucose-induced oxidative stress via the activation of the PI3K/AKT/Nrf2 pathway, and promote bone regeneration in type 1 diabetic rats.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Chrysin Attenuates High Glucose-Induced BMSC Dysfunction via the Activation of the PI3K/AKT/Nrf2 Signaling Pathway

Li¹,

Wang²

2022

DDDT

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“…The GO analysis data indicated that the high expression of DEGs might be implicated in developmental process, cell differentiation, growth factor binding and etc. Many studies have further shown that the impaired propensity to proliferate, the decreased differentiation potential and the declined regenerative capacity may be more evident in stem cells such as MSCs [ 21 , 35 , 36 ], muscle stem cells (MuSCs) [ 37 , 38 ] and HSCs [ 39 , 40 ] from aged individuals. The down-regulated DEGs chiefly participate in metabolism process.…”

Section: Discussionmentioning

confidence: 99%

RNA sequencing profiles reveal dynamic signaling and glucose metabolic features during bone marrow mesenchymal stem cell senescence

Sun

Gao

et al. 2022

Cell Biosci

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Background Stem cell senescence is considered as a significant driver of organismal aging. As individuals age, the number of stem cells is declined, and the ability to proliferate and survive is also weakened. It has been reported that metabolism plays an important role in stem cell self-renewal, multilineage differentiation, senescence and fate determination, which has aroused widespread concerns. However, whether metabolism-related genes or signalling pathways are involved in physiological aging remain largely undetermined. Results In the current study, we showed 868 up-regulated and 2006 down-regulated differentially expressed genes (DEGs) in bone marrow mesenchymal stem cells (MSCs) from old rats in comparison with that from young rats by performing RNA sequence. And DEGs functions and pathways were further selected by function enrichment analysis. The results indicated that the high expression of DEGs might participate in cell differentiation, growth factor binding and etc., while the down-regulated DEGs were majorly enriched in metabolism process, such as the cellular metabolic process and mitochondria. Then, we screened and verified DEGs related to glucose metabolism and investigated the glycolysis levels. We identified that glucose uptake, lactate secretion, ATP production and relative extracellular acidification rates (ECAR) were all diminished in MSCs from old rats. More importantly, we conducted microRNA prediction on the key DEGs of glycolysis to elucidate the potential molecular mechanisms of glucose metabolism affecting MSC senescence. Conclusions Our study unravelled the profiles of DEGs in age-associated MSC senescence and their functions and pathways. We also clarified DEGs related to glucose metabolism and down-regulated glycolysis level in age-associated MSC senescence. This study will uncover the metabolic effects on regulating stem cell senescence, and provide novel therapeutic targets for ameliorating age-associated phenotypes.

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“…RT-qPCR was performed in accordance with a previously published method (Ren et al, 2021). Total RNA was isolated with the miRNeasy Mini Kit (Qiagen, Germany) according to the manufacturer's instructions.…”

Section: Rt-qpcrmentioning

confidence: 99%

Schwann Cell-Derived Exosomes Induce the Differentiation of Human Adipose-Derived Stem Cells Into Schwann Cells

Zhou

Zhao

et al. 2022

Front. Mol. Biosci.

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Adipose-derived stem cells (ADSCs) can differentiate into Schwann cells (SCs) at the site of nerve injury, where Schwann cell-derived exosomes (SC-Exos) are suspected to exert an induction effect. Our study aimed to induce the differentiation of ADSCs in vitro using SC-Exos and to investigate the mechanisms involved through miRNA sequencing. Subcutaneous fat was used to extract ADSCs. Exosomes were extracted from Schwann cell lines (RSC96) using ultracentrifugation and were able to be taken up by human ADSCs. After 8 days of induction of ADSCs by SC-Exos, phenotypic characteristics were observed by examining the expression of SC markers (S100ß, NGFR, MPZ, GFAP) through RT-qPCR, Western blot and immunofluorescence. The RNA and protein expression levels of S100ß, NGFR, MPZ, and GFAP were found to be significantly higher in the SC-Exo induction group than in the uninduced group, which was also consistent with the immunofluorescence results. Additionally, miRNA sequencing was performed on exosome-induced ADSCs, followed by bioinformatic analysis and validation of the results. According to the sequencing results, there were a total of 94 differentially expressed miRNAs. Bioinformatics analysis indicated that 3506 Gene Ontology terms and 98 Kyoto Encyclopedia of Genes and Genomes pathways were significantly enriched. Ten miRNAs, 5 target mRNAs and elevated expression of the PIK3CD/Akt pathway were validated by RT-qPCR or Western blot, which is consistent with the sequencing results. Our study demonstrates that the utility of SC-Exos is effective in inducing the differentiation of ADSCs into SCs, in which these validated differentially expressed miRNAs exert a vital effect. This work provides a new paradigm via rationally applying Schwann cell-derived exosomes as a promising therapeutic option for repairing peripheral nerve injury.

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The whole profiling and competing endogenous RNA network analyses of noncoding RNAs in adipose-derived stem cells from diabetic, old, and young patients

Cited by 33 publications

References 69 publications

Chrysin Attenuates High Glucose-Induced BMSC Dysfunction via the Activation of the PI3K/AKT/Nrf2 Signaling Pathway

Chrysin Attenuates High Glucose-Induced BMSC Dysfunction via the Activation of the PI3K/AKT/Nrf2 Signaling Pathway

RNA sequencing profiles reveal dynamic signaling and glucose metabolic features during bone marrow mesenchymal stem cell senescence

Schwann Cell-Derived Exosomes Induce the Differentiation of Human Adipose-Derived Stem Cells Into Schwann Cells

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