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姜黄素通过端粒酶逆转录酶(TERT)基因表达影响脂肪组织来源的间充质干细胞衰老。

Curcumin Affects Adipose Tissue-Derived Mesenchymal Stem Cell Aging Through TERT Gene Expression.

作者信息

Pirmoradi Samaneh, Fathi Ezzatollah, Farahzadi Raheleh, Pilehvar-Soltanahmadi Younes, Zarghami Nosratollah

机构信息

Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.

出版信息

Drug Res (Stuttg). 2018 Apr;68(4):213-221. doi: 10.1055/s-0043-119635. Epub 2017 Oct 10.

Abstract

Aging and losing cell survival is one of the main problems in cell therapy. Aging of Mesenchymal Stem Cells (MSCs) is associated with a rise in intracellular reactive oxygen species, decrease in telomerase reverse transcriptase (TERT) expression and finally eroded telomere ends. Given that the production of free radicals in the aging process is effective, the use of antioxidants can help in scavenging free radicals and prevent the aging of cells. The aim of this study is to evaluate the effects of curcumin on proliferation, aging and TERT expression of rat adipose tissue-derived stem cells (rADSC). rADSCs were isolated from inguinal rat adipose tissue and their viabilities were assessed by MTT after exposure to different concentrations of curcumin. Flow-cytometry was performed for investigating the cell surface markers. Adipogenic and osteogenic differentiation were carried out to evaluate the pluripotency of rADSCs. Telomerase expression and percentage of senescent cells were evaluated using real-time PCR and senescence-associated β-galactosidase activity, respectively. The results demonstrated significant proliferation of rADSCs after 48 h treatment with 1 and 5 µM curcumin. Additionally, these concentrations could significantly reduce the population doubling time and aging of rADSCs at different passages. The findings of SA-ß-gal staining showed that curcumin significantly decreased the number of senescent cells in the 5 and 7 cell passages. Moreover, expression levels of TERT increased in the presence of 1 and 5 µM curcumin than control group (P<0.001). As a conclusion, curcumin may be a good candidate to improve lifespan of rADSCs through promoting TERT gene expression.

摘要

细胞衰老和细胞存活能力丧失是细胞治疗中的主要问题之一。间充质干细胞(MSCs)的衰老与细胞内活性氧的增加、端粒酶逆转录酶(TERT)表达的降低以及最终端粒末端的侵蚀有关。鉴于衰老过程中自由基的产生具有影响,使用抗氧化剂有助于清除自由基并防止细胞衰老。本研究的目的是评估姜黄素对大鼠脂肪组织来源干细胞(rADSC)增殖、衰老和TERT表达的影响。从腹股沟大鼠脂肪组织中分离出rADSC,并在暴露于不同浓度的姜黄素后通过MTT法评估其活力。进行流式细胞术以研究细胞表面标志物。进行成脂和成骨分化以评估rADSC的多能性。分别使用实时PCR和衰老相关β-半乳糖苷酶活性评估端粒酶表达和衰老细胞百分比。结果表明,用1和5µM姜黄素处理48小时后,rADSC有显著增殖。此外,这些浓度可显著缩短不同传代rADSC的群体倍增时间并减少其衰老。SA-β-半乳糖苷染色结果表明,姜黄素在第5和第7代细胞中显著减少了衰老细胞的数量。此外,与对照组相比,在存在1和5µM姜黄素的情况下,TERT的表达水平有所增加(P<0.001)。总之,姜黄素可能是通过促进TERT基因表达来延长rADSC寿命的良好候选物。

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