3.5 Verification of SI-ALI-associated genes in LOC and Molecular Docking of Key Molecules
Comparison of DEPs from the LOC and in vivo models identified six common genes: EPS15L1, CRIP1, SLC25A10, ATL3, SRP68, and Catechol-O-Methyltransferase (COMT), with only COMT being upregulated in both models (Figures 5C-D). We evaluated mRNA expression levels of COMT and other significantly altered DEPs in the chip model, including Dedicator of cytokinesis 2 (DOCK2), thiosulfate sulfurtransferase (TST), Keratinocyte Growth Factor Receptor-Related Protein 1 (KRR1), nitrilase-like protein 1 (NIT1), and RAP1 GTPase-GDP dissociation stimulator 1 (RAP1GDS1) (Figure 6A). The expression of COMT and DOCK2 was upregulated in both epithelial and endothelial cells in the smoke exposure group (Figures 6A-a, f), consistent with the proteomic findings. Moreover, mRNA expression levels of TST, NIT1, and RAP1GDS1 corresponded with the proteomic data (Figures 6A-b, d, e). Additionally, KRR1 showed upregulation in the epithelium following smoke exposure, with no significant change in the endothelium (Figure 6C-c). These results demonstrate that the identified molecules are consistent at both transcriptional and translational levels, except for KRR1.
To further explore therapeutic drugs, we employed computational biology to perform molecular docking of COMT with potential drugs. The results indicated that several FDA-approved drugs, including Ractopamine HCl, Bimatoprost, Ibutilide Fumarate, Fenoterol, Prucalopride Succinate, and Fenoterol hydrobromide, may have therapeutic effects (Figure 6B).