Disease types and pathogenic mechanisms induced by PM_2.5 in five human systems: An analysis using omics and human disease databases

Atmospheric fine particulate matter (PM_2.5) 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 PM_2.5 in various human systems remain unclear. In this study, the disease types induced by PM_2.5 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 PM_2.5 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 PM_2.5 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 PM_2.5 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 PM_2.5. 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. PM_2.5 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 PM_2.5-related disease types and is an important supplement to epidemiological investigation. It clarifies the risks of PM_2.5 exposure, elucidates the pathogenic mechanisms, and provides scientific support for promoting the precise prevention and treatment of PM_2.5-related diseases.