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miR-146a 在人牙周膜细胞中受高糖诱导的氧化应激的相互调节。

MiR-146a Is Mutually Regulated by High Glucose-Induced Oxidative Stress in Human Periodontal Ligament Cells.

机构信息

Department of Periodontology, Osaka Dental University, 8-1, Kuzuhahanazono-cho, Hirakata 573-1121, Osaka, Japan.

出版信息

Int J Mol Sci. 2024 Oct 4;25(19):10702. doi: 10.3390/ijms251910702.

Abstract

The high-glucose conditions caused by diabetes mellitus (DM) exert several effects on cells, including inflammation. miR-146a, a kind of miRNA, is involved in inflammation and may be regulated mutually with reactive oxygen species (ROS), which are produced under high-glucose conditions. In the present study, we used human periodontal ligament cells (hPDLCs) to determine the effects of the high-glucose conditions of miR-146a and their involvement in the regulation of oxidative stress and inflammatory cytokines using Western blotting, PCR, ELISA and other methods. When hPDLCs were subjected to high glucose (24 mM), cell proliferation was not affected; inflammatory cytokine expression, ROS induction, interleukin-1 receptor-associated kinase 1 (IRAK1) and TNF receptor-associated factor 6 (TRAF6) expression increased, but miR-146a expression decreased. Inhibition of ROS induction with the antioxidant N-acetyl-L-cysteine restored miR-146a expression and decreased inflammatory cytokine expression compared to those under high-glucose conditions. In addition, overexpression of miR-146a significantly suppressed the expression of the inflammatory cytokines IRAK1 and TRAF6, regardless of the glucose condition. Our findings suggest that oxidative stress and miR-146a expression are mutually regulated in hPDLCs under high-glucose conditions.

摘要

糖尿病引起的高葡萄糖环境对细胞产生多种影响,包括炎症。miR-146a 是一种 miRNA,参与炎症反应,可能与高葡萄糖条件下产生的活性氧 (ROS) 相互调节。在本研究中,我们使用人牙周膜细胞 (hPDLCs) 通过 Western blot、PCR、ELISA 等方法,确定 miR-146a 在高葡萄糖条件下的作用及其对氧化应激和炎症细胞因子调节的影响。当 hPDLCs 处于高葡萄糖 (24mM) 时,细胞增殖不受影响;炎症细胞因子表达、ROS 诱导、白细胞介素-1 受体相关激酶 1 (IRAK1) 和肿瘤坏死因子受体相关因子 6 (TRAF6) 表达增加,但 miR-146a 表达减少。用抗氧化剂 N-乙酰-L-半胱氨酸抑制 ROS 诱导可恢复 miR-146a 的表达,并降低炎症细胞因子的表达,与高葡萄糖条件下的表达相比。此外,miR-146a 的过表达可显著抑制炎症细胞因子 IRAK1 和 TRAF6 的表达,而与葡萄糖条件无关。我们的研究结果表明,在高葡萄糖条件下,hPDLCs 中的氧化应激和 miR-146a 表达相互调节。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3212/11476635/9179317c085b/ijms-25-10702-g001.jpg

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