Integrative Genomic and Transcriptomic Analysis in Acute Interstitial Pneumonia

• Published in: Journal of cellular and molecular medicine 2024-12, Vol.28 (23), p.e70252-n/a
• Main Authors: Kwak, Donghee, Kang, Junho, Yu, Yeuni, Lee, Hansong, Kim, Yeongjoo, Kwon, Eun Jung, Lim, Dong Min, Mun, Seongik, Kim, Hyo Min, Lee, Hae Seul, Kim, Yun Hak, Yeo, Hye Ju, Cho, Woo Hyun
• Format: Article
• Language: English
• Subjects: Acute Disease; acute interstitial pneumonia; Aged; Biobanks; Down-regulation; expression quantitative trait loci; Extracellular matrix; Female; Fibrosis; Gene expression; Gene Expression Profiling; Gene Expression Regulation; Gene regulation; Genetic analysis; Genomes; Genomic analysis; Genomics; Genomics - methods; Genotypes; Humans; Keratin; Lung - metabolism; Lung - pathology; Lung diseases; Lung Diseases, Interstitial - genetics; Lung transplants; Male; Middle Aged; Mutation; Mutation - genetics; Original; Patients; Pneumonia; Polymorphism, Single Nucleotide - genetics; Quantitative Trait Loci; Single-nucleotide polymorphism; Therapeutic targets; Transcriptome - genetics; Transcriptomics; whole genome sequencing
• ISSN: 1582-1838; 1582-4934; 1582-4934
• DOI: 10.1111/jcmm.70252

ABSTRACT Acute Interstitial Pneumonia (AIP) represents a severe form of diffuse lung injury within the idiopathic interstitial pneumonia spectrum. Given the limited understanding of its molecular basis, this study aims to elucidate AIP's genomic and transcriptomic profiles to uncover its pathophysiological underpinnings and identify potential therapeutic targets. We conducted a comprehensive analysis of genomic and transcriptomic data from lung tissues of 15 AIP patients. This included assessing differentially expressed genes (DEGs) and identifying mutations in exonic coding variants, as well as analysing expression quantitative trait loci (eQTL) profiles to link non‐coding SNP genotypes with gene expression levels. Transcriptomic analysis revealed a significant upregulation of genes linked to the Type I interferon receptor and keratin filament, and a downregulation of genes related to focal adhesion and endothelial integrity, compared to healthy individuals. These patterns were distinct from those observed in idiopathic pulmonary fibrosis (IPF) and non‐IPF interstitial lung diseases (ILDs). Genomic analysis highlighted mutations in genes associated with keratin and the extracellular matrix. Additionally, eQTL profiling provided insights into the genetic regulation of gene expression in AIP. Our findings reveals AIP's unique molecular landscape, differentiating it from other ILDs and laying the groundwork for future diagnostic and therapeutic research.