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基于大鼠模型 DNA 甲基化和 RNA 测序数据的综合分析，探讨颗粒物对肌腱愈合的影响及机制。

Effects and Mechanism of Particulate Matter on Tendon Healing Based on Integrated Analysis of DNA Methylation and RNA Sequencing Data in a Rat Model.

机构信息

Myunggok Medical Research Institute, College of Medicine, Konyang University, Daejeon 35365, Korea.

Division of Pulmonology, Department of Internal Medicine, Konyang University Hospital, Daejeon 35365, Korea.

出版信息

Int J Mol Sci. 2022 Jul 25;23(15):8170. doi: 10.3390/ijms23158170.

DOI:10.3390/ijms23158170
PMID:35897746
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9332732/
Abstract

Exposure to particulate matter (PM) has been linked with the severity of various diseases. To date, there is no study on the relationship between PM exposure and tendon healing. Open Achilles tenotomy of 20 rats was performed. The animals were divided into two groups according to exposure to PM: a PM group and a non-PM group. After 6 weeks of PM exposure, the harvest and investigations of lungs, blood samples, and Achilles tendons were performed. Compared to the non-PM group, the white blood cell count and tumor necrosis factor-alpha expression in the PM group were significantly higher. The Achilles tendons in PM group showed significantly increased inflammatory outcomes. A TEM analysis showed reduced collagen fibrils in the PM group. A biomechanical analysis demonstrated that the load to failure value was lower in the PM group. An upregulation of the gene encoding cyclic AMP response element-binding protein (CREB) was detected in the PM group by an integrated analysis of DNA methylation and RNA sequencing data, as confirmed via a Western blot analysis showing significantly elevated levels of phosphorylated CREB. In summary, PM exposure caused a deleterious effect on tendon healing. The molecular data indicate that the action mechanism of PM may be associated with upregulated CREB signaling.

摘要

颗粒物 (PM) 暴露与各种疾病的严重程度有关。迄今为止，尚无关于 PM 暴露与肌腱愈合之间关系的研究。对 20 只大鼠进行开放性跟腱切断术。根据暴露于 PM 的情况将动物分为两组：PM 组和非 PM 组。暴露于 PM 6 周后，进行肺、血液样本和跟腱的收获和调查。与非 PM 组相比，PM 组的白细胞计数和肿瘤坏死因子-α表达明显更高。PM 组的跟腱显示出明显增加的炎症反应。TEM 分析显示 PM 组的胶原纤维明显减少。生物力学分析表明，PM 组的失效负荷值较低。通过 DNA 甲基化和 RNA 测序数据的综合分析检测到 PM 组中编码环磷酸腺苷反应元件结合蛋白 (CREB) 的基因上调，通过 Western blot 分析证实磷酸化 CREB 水平显著升高。总之，PM 暴露对肌腱愈合造成有害影响。分子数据表明，PM 的作用机制可能与上调的 CREB 信号有关。

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