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硫化氢通过TRPV4通道介导的钙内流减轻人牙周膜干细胞衰老。

Hydrogen Sulphide Alleviates Senescence of Human Periodontal Ligament Stem Cells by TRPV4 Channel Mediated Calcium Flux.

作者信息

Zhou Yi Kun, Yang Rui Li, Liu Xiao Mo

出版信息

Chin J Dent Res. 2023 Mar 29;26(1):19-27. doi: 10.3290/j.cjdr.b3978645.

Abstract

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.

摘要

目的

探讨硫化氢(H2S)是否能保护人牙周膜干细胞(PDLSCs)免于衰老及其潜在机制。

方法

采用细胞周期分析和Ki-67检测来测量PDLSCs的增殖。运用实时聚合酶链反应(PCR)检测细胞衰老相关的p16和p21。通过测量Ca2+成像检测钙内流。此外,我们利用基因芯片分析H2S作用于PDLSCs的潜在机制。

结果

衰老的PDLSCs细胞增殖率显著降低。衰老的PDLSCs中细胞衰老相关的p16和p21表达显著增加。硫化氢供体(GYY4137)处理提高了衰老PDLSCs的增殖率。此外,硫化氢供体处理有效防止了衰老过程中PDLSCs的细胞周期停滞,并抑制了细胞衰老相关标志物的表达。机制上,硫化氢供体处理可激活PDLSCs中的钙内流。此外,用TRPV4抑制剂预处理可显著减弱硫化氢供体处理诱导的PDLSCs钙内流。它还减轻了硫化氢对PDLSCs衰老的保护作用。

结论

硫化氢通过TRPV4通道介导的钙通量减轻人PDLSCs的衰老。这些结果为应对细胞衰老提供了一种潜在策略,并可能促进口腔疾病的细胞治疗。

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