大气细颗粒物(PM2.5)会危害人体的各个系统。由于目前对流行病学和毒理学理解的局限性,PM2.5在各种人类系统中引起的疾病类型和致病机制尚不清楚。在这项研究中,PM2.5在呼吸道引起的疾病类型,循环,内分泌,女性和男性泌尿生殖系统已被研究,并在分子水平上确定了致病机制。结果表明,PM2.5极有可能诱发肺气肿,再灌注损伤,恶性甲状腺肿瘤,卵巢子宫内膜异位症,和肾炎分别在上述每个系统中。最重要的共存基因,细胞成分,生物过程,分子功能,PM2.5靶向的五个系统中的通路是Fos原癌基因(FOS),细胞外基质,泌尿生殖系统发育,赋予拉伸强度的细胞外基质结构成分,和铁性分别。每个系统中PM2.5显著且独特靶向的差异表达基因是BTG2(呼吸),BIRC5(循环),NFE2L2(内分泌),TBK1(女性泌尿生殖系统)和STAT1(男性泌尿生殖系统)。重要的疾病相关细胞成分,生物过程,和分子功能是由PM2.5特异性诱导的。例如,对受伤的反应,血管形态发生,身体形态发生,对内质网应激的负调节,和对I型干扰素的反应分别是每个系统中最独特的生物过程。PM2.5主要作用于肿瘤(呼吸道)的PD-L1表达和PD-1检查点通路等关键疾病相关通路,细胞周期(循环),凋亡(内分泌),抗原加工和呈递(女性泌尿生殖系统),和神经活性配体-受体相互作用(男性泌尿生殖系统)。本研究为阐明PM2.5相关疾病类型提供了新的分析策略,是流行病学调查的重要补充。它阐明了PM2.5暴露的风险,阐明致病机制,为推动PM2.5相关疾病精准防治提供科学支撑。
Atmospheric fine particulate matter (PM2.5) can harm various systems in the human body. Due to limitations in the current understanding of epidemiology and toxicology, the disease types and pathogenic mechanisms induced by PM2.5 in various human systems remain unclear. In this study, the disease types induced by PM2.5 in the respiratory, circulatory, endocrine, and female and male urogenital systems have been investigated and the pathogenic mechanisms identified at molecular level. The results reveal that PM2.5 is highly likely to induce pulmonary emphysema, reperfusion injury, malignant thyroid neoplasm, ovarian endometriosis, and nephritis in each of the above systems respectively. The most important co-existing gene, cellular component, biological process, molecular function, and pathway in the five systems targeted by PM2.5 are Fos proto-oncogene (FOS), extracellular matrix, urogenital system development, extracellular matrix structural constituent conferring tensile strength, and ferroptosis respectively. Differentially expressed genes that are significantly and uniquely targeted by PM2.5 in each system are BTG2 (respiratory), BIRC5 (circulatory), NFE2L2 (endocrine), TBK1 (female urogenital) and STAT1 (male urogenital). Important disease-related cellular components, biological processes, and molecular functions are specifically induced by PM2.5. For example, response to wounding, blood vessel morphogenesis, body morphogenesis, negative regulation of response to endoplasmic reticulum stress, and response to type I interferon are the top uniquely existing biological processes in each system respectively. PM2.5 mainly acts on key disease-related pathways such as the PD-L1 expression and PD-1 checkpoint pathway in cancer (respiratory), cell cycle (circulatory), apoptosis (endocrine), antigen processing and presentation (female urogenital), and neuroactive ligand-receptor interaction (male urogenital). This study provides a novel analysis strategy for elucidating PM2.5-related disease types and is an important supplement to epidemiological investigation. It clarifies the risks of PM2.5 exposure, elucidates the pathogenic mechanisms, and provides scientific support for promoting the precise prevention and treatment of PM2.5-related diseases.