mTOR Inhibition Rejuvenates the Aging Gingival Fibroblasts through Alleviating Oxidative Stress.
mTOR Inhibition Rejuvenates the Aging Gingival Fibroblasts through Alleviating Oxidative Stress.
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mTOR 抑制通过减轻氧化应激使老化的牙龈成纤维细胞恢复活力
DOI：
10.1155/2017/6292630
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发表时间：
2017
影响因子：
--
通讯作者：
Shu R
中科院分区：
文献类型：
--
作者：
Xia Y;Sun M;Xie Y;Shu R
随着牙周组织的老化，牙周组织对牙周致病菌的抵抗力下降，对炎症反应减弱，易发生肿瘤。人牙龈成纤维细胞（hGFs）通过连续复制培养作为体外老化的替代品。为了研究雷帕霉素（mTOR）抑制机制对老化牙龈的影响，我们用雷帕霉素（20 nmol/L）刺激高传代hGFs 3天和30天。采用免疫荧光、实时荧光定量PCR、ELISA、Western blotting和流式细胞术检测细胞和生物学变化。数据表明，抑制mTOR信号导致更少的衰老相关β-半乳糖苷酶-（SA-β-Gal-）阳性细胞，延迟衰老的开始，保持增殖能力，并降低相关衰老相关标志物的表达水平，如p16 INK 4a、p21 CIP 1a、白细胞介素-6（IL-6）和IL-8。此外，当感染的主要牙周病原体，牙龈卟啉单胞菌（ATCC 33277），雷帕霉素预处理组减少炎症细胞因子（IL-6和IL-8）的表达与对照组相比。mTOR抑制上调抗氧化成分（Cat、Sod 2和Prdx 3; P < 0.05）的基因表达，从而中和过量的活性氧（ROS）。总之，我们的研究结果表明，mTOR抑制可能在一定程度上使老化的牙龈年轻化，并通过消除氧化应激来减轻炎症。
The aging periodontium may be vulnerable to periodontal pathogens and poor response to inflammation and susceptible to tumorigenesis. Human gingival fibroblasts (hGFs) through continuously replicative culture served as an in vitro surrogate for aging. To investigate the effects of the mechanistic target of rapamycin (mTOR) inhibition on the aging gingiva, we stimulated the high-passage hGFs with rapamycin (20 nmol/L) for 3 days and 30 days. The cellular and biological changes were examined by immunofluorescence, real-time PCR, ELISA, Western blotting, and flow cytometry. The data demonstrated that the inhibition of mTOR signaling led to fewer senescence-associated beta-galactosidase- (SA-β-Gal-) positive cells, delayed the onset of senescence, preserved the capability of proliferation, and lowered the expression levels of relevant senescence-associated markers, such as p16INK4a, p21CIP1a, interleukin-6 (IL-6), and IL-8. In addition, when infected by prominent periodontal pathogens, Porphyromonas gingivalis (ATCC 33277), rapamycin-pretreated groups decreased the expression of inflammatory cytokines (IL-6 and IL-8) compared with the control group. mTOR inhibition upregulated the gene expression of antioxidant components (Cat, Sod2, and Prdx3; P < 0.05) and consequently neutralized the excessive reactive oxygen species (ROS). In conclusion, our results indicated that mTOR inhibition might rejuvenate the aging gingiva to some extent and relieve inflammation through eliminating oxidative stress.
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影响因子：
168.9
作者：
Christensen, Kaare;Doblhammer, Gabriele;Rau, Roland;Vaupel, James W.
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Vaupel, James W.
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18.6
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Yakar S
影响因子：
3.9
作者：
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通讯作者：
Orihuela, Carlos J.
影响因子：
4.3
作者：
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