硫化氢通过TRPV4通道介导的钙通量缓解人牙周韧带干细胞衰老。

Yi Kun Zhou, Rui Li Yang, Xiao Mo Liu
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引用次数: 0

摘要

目的:探讨硫化氢(H2S)对人牙周韧带干细胞(PDLSCs)衰老的保护作用及其可能的机制。方法:采用细胞周期法和Ki-67法检测PDLSCs的增殖。实时聚合酶链反应(Real-time polymerase chain reaction, PCR)检测细胞衰老相关的p16和p21。通过钙离子成像检测钙内流。此外,我们通过微阵列分析了H2S作用于PDLSCs的可能机制。结果:衰老后的PDLSCs细胞增殖速率明显降低。衰老的PDLSCs中与细胞衰老相关的p16和p21的表达显著增加。H2S供体(GYY4137)处理可提高衰老PDLSCs的增殖率。此外,H2S处理的供体有效地阻止了衰老过程中PDLSCs的细胞周期阻滞,抑制了细胞衰老相关标志物的表达。机械上,H2S供体处理可以激活PDLSCs中的钙内流。此外,TRPV4抑制剂预处理可显著减弱H2S供体处理诱导的PDLSCs钙内流。H2S对PDLSCs衰老的保护作用也有所减轻。结论:H2S通过TRPV4通道介导的钙通量减轻人PDLSCs的衰老。这些结果为处理细胞衰老提供了一种潜在的策略,并可能促进口腔疾病的细胞治疗。
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Hydrogen Sulphide Alleviates Senescence of Human Periodontal Ligament Stem Cells by TRPV4 Channel Mediated Calcium Flux.

Objective: To explore whether hydrogen sulphide (H2S) could protect human periodontal ligament stem cells (PDLSCs) from senescence and the possible underlying mechanisms.

Methods: Cell cycle assay and Ki-67 assay were used to measure proliferation of PDLSCs. Real-time polymerase chain reaction (PCR) was used to measure cellular senescence-related p16 and p21. Calcium influx was detected by measurement of Ca2+ imaging. In addition, we analysed the possible mechanisms underlying H2S acting on PDLSCs by microarray.

Results: The cell proliferation rate of aging PDLSCs decreased significantly. The expression of cellular senescence-related p16 and p21 significantly increased in aging PDLSCs. H2S donor (GYY4137) treatment increased the proliferation rate of senescence PDLSCs. Furthermore, the donor of H2S treatment effectively prevented cell cycle arrest of PDLSCs during the aging process and inhibited the expression of cellular senescence-related markers. Mechanically, H2S donor treatment could activate the calcium influx in PDLSCs. Moreover, pretreatment with TRPV4 inhibitors significantly attenuated the calcium influx induced by H2S donor treatment in PDLSCs. It also alleviated the protective effect of H2S on the senescence of PDLSCs.

Conclusion: H2S alleviated the senescence of human PDLSCs by TRPV4 channel mediated calcium flux. These results provide a potential strategy to deal with cell aging and may facilitate cell therapy for oral diseases.

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