The gene expression of CALD1, CDH2, and POSTN in fibroblast are related to idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is characterized by progressive lung dysfunction due to excessive collagen production and tissue scarring. Despite recent advancements, the molecular mechanisms remain unclear. RNA sequencing identified 475 differentially expressed genes (DEGs) in the TGF-β1-induced primary lung fibrosis model. Gene expression chips GSE101286 and GSE110147 from NCBI gene expression omnibus (GEO) database were analyzed using GEO2R, revealing 94 DEGs in IPF lung tissue samples. The gene ontology (GO) and pathway enrichment, Protein-protein interaction (PPI) network construction, and Maximal Clique Centrality (MCC) scoring were performed. Experimental validation included RT-qPCR, Immunohistochemistry (IHC), and Western Blot, with siRNA used for gene knockdown. A co-expression network was constructed by GeneMANIA. GO enrichment highlighted significant enrichment of DEGs in TGF-β cellular response, connective tissue development, extracellular matrix components, and signaling pathways such as the AGE-RAGE signaling pathway and ECM-receptor interaction. PPI network analysis identified hub genes, including FN1, COL1A1, POSTN, KIF11, and ECT2. CALD1 (Caldesmon 1), CDH2 (Cadherin 2), and POSTN (Periostin) were identified as dysregulated hub genes in both the RNA sequencing and GEO datasets. Validation experiments confirmed the upregulation of CALD1, CDH2, and POSTN in TGF-β1-treated fibroblasts and IPF lung tissue samples. IHC experiments probed tissue-level expression patterns of these three molecules. Knockdown of CALD1, CDH2, and POSTN attenuated the expression of fibrotic markers (collagen I and α-SMA) in response to TGF-β1 stimulation in primary fibroblasts. Co-expression analysis revealed interactions between hub genes and predicted genes involved in actin cytoskeleton regulation and cell-cell junction organization. CALD1, CDH2, and POSTN, identified as potential contributors to pulmonary fibrosis, present promising therapeutic targets for IPF patients. Copyright © 2024 Wu, Liu, Zhang, Ye, Gu, Jiang, Zhu, Ye, Li, Huang and Cao.

Citation

Shufei Wu, Mengying Liu, Mingrui Zhang, Xu Ye, Huimin Gu, Cheng Jiang, Huihui Zhu, Xiaoling Ye, Qi Li, Xinmei Huang, Mengshu Cao. The gene expression of CALD1, CDH2, and POSTN in fibroblast are related to idiopathic pulmonary fibrosis. Frontiers in immunology. 2024;15:1275064

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PMID: 38370408

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