LIMK1 and PKM as Integratively Identified Transcriptomic Signatures in Inflammatory Bowel Disease

Inflammatory bowel disease (IBD) involves complex immunometabolic dysregulation. Mitochondria-associated endoplasmic reticulum membranes (MAMs) link metabolic adaptation and inflammatory signaling, but gene expression features associated with MAM-related transcriptomic states in IBD remain unclear. Public transcriptomic datasets were integrated with a curated MAM-related gene set and herbal target information. Differential expression analysis, weighted gene coexpression network analysis, and machine learning-assisted feature selection were used to identify candidate genes. A two-gene nomogram was constructed and evaluated in discovery and independent validation datasets. Functional enrichment, immune deconvolution, regulatory network prediction, molecular docking, 200-ns molecular dynamics simulations, and preliminary quantitative polymerase chain reaction validation were performed. LIMK1 and PKM were identified as candidate transcriptomic signature genes associated with IBD status and MAM-related transcriptional states, showing discriminatory performance in independent datasets. Both genes were associated with cytokine-cytokine receptor interaction and drug metabolism-cytochrome P450 pathways and were linked to macrophage-related immune states. Structural analyses suggested stable predicted binding between PKM and 1-(4-hydroxybenzyl)-4-methoxy-9,10-dihydrophenanthrene-2,7-diol and structurally plausible interactions between LIMK1 and palmatine. Preliminary tissue-level validation supported the disease-associated expression pattern of PKM, whereas LIMK1 showed a consistent but nonsignificant upward trend. LIMK1 and PKM may represent candidate transcriptomic signatures associated with MAM-related regulatory states in IBD. These findings should be interpreted as hypothesis-generating associations rather than evidence of MAM localization, functional causality, or therapeutic efficacy. Further protein-level and functional validation is required.