Cigarette smoke exposure upregulates peripheral blood mRNA levels of ITGA2B, TIMP1, JAK2, and STAT3 and increases platelet count in rats: implications for the thrombocytosis and ET-related molecular alterations

To investigate cigarette smoke exposure as an environmental risk factor in Essential Thrombocythemia(ET) and validate key regulated target genes, we integrated peripheral blood transcriptomic data from ET patients with the Comparative Toxicogenomics Database(CTD) to screen for Environmental pollutants(EPs) and target genes. Key genes were identified via protein-protein interaction(PPI) network analysis, and their binding affinities with Nicotine , a component of cigarette smoke, were simulated through molecular docking. An 8-week cigarette smoke exposure model was established in SD rats to monitor dynamic changes in target gene mRNA expression(qRT-PCR) and platelet counts. Bioinformatics analysis identified 558 differentially expressed genes and 17 EPs, highlighting Nicotine and reactive oxygen species(ROS) as crucial factors. Molecular docking revealed strong binding between Nicotine and ITGA2B(-6.7 kcal/mol) and TIMP1(-6.0 kcal/mol). In rats, cigarette smoke exposure significantly upregulated ITGA2B, TIMP1(from week 6, p < 0.05) and JAK2, STAT3(from week 4, p < 0.05), which correlated with increased platelet counts ( p = 0.041). Our study demonstrated that cigarette smoke exposure induced platelet proliferation mediated by ITGA2B and TIMP1. Furthermore, the upregulation of JAK2 and STAT3 might be associated with excessive platelet production. These findings suggest that controlling cigarette smoke exposure might be useful in preventing thrombocytosis both in healthy and ET subjects.