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

Area of Science:

• Immunometabolism
• Transcriptomics
• Molecular Biology

Background:

• Inflammatory bowel disease (IBD) is characterized by immunometabolic dysregulation.
• Mitochondria-associated endoplasmic reticulum membranes (MAMs) are crucial in linking metabolic adaptation and inflammatory signaling.
• Gene expression patterns related to MAMs in IBD are not well understood.

Purpose of the Study:

• To identify transcriptomic signatures associated with MAM-related states in IBD.
• To explore the potential of LIMK1 and PKM as biomarkers for IBD.

Main Methods:

• Integration of public transcriptomic datasets with MAM-related gene sets.
• Differential gene expression analysis, weighted gene coexpression network analysis, and machine learning.
• Construction and validation of a two-gene nomogram.
• Functional enrichment, immune deconvolution, network prediction, molecular docking, and molecular dynamics simulations.

Main Results:

• LIMK1 and PKM were identified as candidate transcriptomic signature genes associated with IBD and MAM states.
• These genes demonstrated discriminatory performance in independent datasets.
• Both genes are linked to cytokine-cytokine receptor interactions, drug metabolism pathways, and macrophage-related immune states.
• Molecular docking and simulations suggested potential interactions with herbal compounds.

Conclusions:

• LIMK1 and PKM may serve as candidate transcriptomic signatures in IBD related to MAM regulatory states.
• These findings are hypothesis-generating and require further protein-level and functional validation.
• The study highlights potential molecular targets for IBD research.