Mescoli Ada, Maffei Giangabriele, Pillo Gelsomina, Bortone Giuseppe, Marchesi Stefano, Morandi Elena, Ranzi Andrea, Rotondo Francesca, Serra Stefania, Vaccari Monica, Zauli Sajani Stefano, Mascolo Maria Grazia, Jacobs Miriam Naomi, Colacci Annamaria
Department of Experimental, Diagnostic and Specialty Medicine, Section of Cancerology, University of Bologna, Bologna, Italy.
Agency for Prevention, Environment and Energy (Arpae), Emilia-Romagna, Italy.
Front Genet. 2020 Nov 9;11:579964. doi: 10.3389/fgene.2020.579964. eCollection 2020.
As the novel coronavirus disease sweeps across the world, there is growing speculation on the role that atmospheric factors may have played on the different distribution of SARS-CoV-2, and on the epidemiological characteristics of COVID-19. Knowing the role that environmental factors play in influenza virus outbreaks, environmental pollution and, in particular, atmospheric airborne (particulate matter, PM) has been considered as a potential key factor in the spread and mortality of COVID-19. A possible role of the PM as the virus carrier has also been debated. The role of PM in exacerbating respiratory and cardiovascular disease has been well recognized. Accumulating evidence support the hypothesis that PM can trigger inflammatory response at molecular, cellular and organ levels. On this basis, we developed the hypothesis that PM may play a role as a booster of COVID-19 rather than as a carrier of SARS-CoV-2. To support our hypothesis, we analyzed the molecular signatures detected in cells exposed to PM samples collected in one of the most affected areas by the COVID-19 outbreak, in Italy. T47D human breast adenocarcinoma cells were chosen to explore the global gene expression changes induced by the treatment with organic extracts of PM 2.5. The analysis of the KEGG's pathways showed modulation of several gene networks related to the leucocyte transendothelial migration, cytoskeleton and adhesion system. Three major biological process were identified, including coagulation, growth control and immune response. The analysis of the modulated genes gave evidence for the involvement of PM in the endothelial disease, coagulation disorders, diabetes and reproductive toxicity, supporting the hypothesis that PM, directly or through molecular interplay, affects the same molecular targets as so far known for SARS-COV-2, contributing to the cytokines storm and to the aggravation of the symptoms triggered by COVID-19. We provide evidence for a plausible cooperation of receptors and transmembrane proteins, targeted by PM and involved in COVID-19, together with new insights into the molecular interplay of chemicals and pathogens that could be of importance for sustaining public health policies and developing new therapeutic approaches.
随着新型冠状病毒病席卷全球,人们越来越多地猜测大气因素可能对严重急性呼吸综合征冠状病毒2(SARS-CoV-2)的不同分布以及新型冠状病毒肺炎(COVID-19)的流行病学特征产生了影响。鉴于了解环境因素在流感病毒爆发中的作用,环境污染,尤其是大气中的空气传播物(颗粒物,PM)被认为是COVID-19传播和致死率的一个潜在关键因素。PM作为病毒载体的可能作用也一直存在争议。PM在加重呼吸道和心血管疾病方面的作用已得到充分认识。越来越多的证据支持这样的假设,即PM可在分子、细胞和器官水平引发炎症反应。在此基础上,我们提出了一个假设,即PM可能是COVID-19的助推器,而不是SARS-CoV-2的载体。为了支持我们的假设,我们分析了在意大利COVID-19疫情最严重地区之一采集的PM样本处理的细胞中检测到的分子特征。选择T47D人乳腺腺癌细胞来探索PM 2.5有机提取物处理诱导的全球基因表达变化。京都基因与基因组百科全书(KEGG)通路分析显示,与白细胞跨内皮迁移、细胞骨架和黏附系统相关的几个基因网络受到调节。确定了三个主要生物学过程,包括凝血、生长控制和免疫反应。对这些受调节基因的分析证明PM参与了内皮疾病、凝血障碍、糖尿病和生殖毒性,支持了这样的假设,即PM直接或通过分子相互作用,影响了迄今为止已知的SARS-CoV-2的相同分子靶点,导致细胞因子风暴,并加剧了COVID-19引发的症状。我们提供了证据,证明了受PM靶向并参与COVID-19的受体和跨膜蛋白之间可能存在的协同作用,以及对化学物质和病原体分子相互作用的新见解,这对于维持公共卫生政策和开发新的治疗方法可能具有重要意义。