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).