Abu-Elmagd Muhammad, Alghamdi Mansour A, Shamy Magdy, Khoder Mamdouh I, Costa Max, Assidi Mourad, Kadam Roaa, Alsehli Haneen, Gari Mamdooh, Pushparaj Peter Natesan, Kalamegam Gauthaman, Al-Qahtani Mohammed H
Center of Excellence in Genomic Medicine Research, King Abdulaziz University, P.O. Box 80216, Jeddah 21589, Saudi Arabia.
Department of Environmental Sciences, Faculty of Meteorology, Environment and Arid Land Agriculture, King Abdulaziz University, P.O. Box 80208, Jeddah 21589, Saudi Arabia.
Int J Environ Res Public Health. 2017 Apr 20;14(4):440. doi: 10.3390/ijerph14040440.
Particulate matter (PM) contains heavy metals that affect various cellular functions and gene expression associated with a range of acute and chronic diseases in humans. However, the specific effects they exert on the stem cells remain unclear. Here, we report the effects of PM collected from the city of Jeddah on proliferation, cell death, related gene expression and systems of biological analysis in bone marrow mesenchymal stem cells (BM-MSCs), with the aim of understanding the underlying mechanisms. PM and PM were tested in vitro at various concentrations (15 to 300 µg/mL) and durations (24 to 72 h). PMs induced cellular stress including membrane damage, shrinkage and death. Lower concentrations of PM increased proliferation of BM-MSCs, while higher concentrations served to decrease it. PM decreased BM-MSCs proliferation in a concentration-dependent manner. The X-ray fluorescence spectrometric analysis showed that PM contains high levels of heavy metals. Ingenuity Pathway Analysis (IPA) and hierarchical clustering analyses demonstrated that heavy metals were associated with signaling pathways involving cell stress/death, cancer and chronic diseases. qRT-PCR results showed differential expression of the apoptosis genes (BCL2, BAX); inflammation associated genes (TNF-α and IL-6) and the cell cycle regulation gene (p53). We conclude that PM causes inflammation and cell death, and thereby predisposes to chronic debilitating diseases.
颗粒物(PM)含有重金属,这些重金属会影响各种细胞功能以及与人类一系列急慢性疾病相关的基因表达。然而,它们对干细胞产生的具体影响仍不清楚。在此,我们报告了从吉达市采集的PM对骨髓间充质干细胞(BM-MSCs)增殖、细胞死亡、相关基因表达及生物分析系统的影响,旨在了解其潜在机制。在体外对不同浓度(15至300µg/mL)和不同时长(24至72小时)的PM进行了测试。PM诱导了包括膜损伤、细胞收缩和死亡在内的细胞应激。较低浓度的PM可增加BM-MSCs的增殖,而较高浓度则会使其增殖减少。PM以浓度依赖性方式降低BM-MSCs的增殖。X射线荧光光谱分析表明,PM含有高水平的重金属。 Ingenuity通路分析(IPA)和层次聚类分析表明,重金属与涉及细胞应激/死亡、癌症和慢性疾病的信号通路相关。定量逆转录聚合酶链反应(qRT-PCR)结果显示凋亡基因(BCL2、BAX)、炎症相关基因(TNF-α和IL-6)以及细胞周期调控基因(p53)存在差异表达。我们得出结论,PM会引发炎症和细胞死亡,从而使人易患慢性衰弱性疾病。