Integrative omics analysis identifies biomarkers of idiopathic pulmonary fibrosis

特发性肺纤维化 转录组 细胞外基质 生物 肺纤维化 纤维化 蛋白质组学 免疫系统 癌症研究 基因表达 细胞生物学 基因 免疫学 病理 医学 遗传学 内科学
作者
Peiyan Zheng,Shixue Sun,Jingxian Wang,Zhangkai J. Cheng,Kuan Cheok Lei,Mingshan Xue,Teng Zhang,Huimin Huang,Xiaohua Douglas Zhang,Baoqing Sun
出处
期刊:Cellular and Molecular Life Sciences [Springer Nature]
卷期号:79 (1) 被引量:10
标识
DOI:10.1007/s00018-021-04094-0
摘要

Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease characterized by chronic progressive pulmonary fibrosis and a poor prognosis. Genetic studies, including transcriptomic and proteomics, have provided new insight into revealing mechanisms of IPF. Herein we provided a novel strategy to identify biomarkers by integrative analysis of transcriptomic and proteomic profiles of IPF patients. We examined the landscape of IPF patients' gene expression in the transcription and translation phases and investigated the expression and functions of two new potential biomarkers. Differentially expressed (DE) mRNAs were mainly enriched in pathways associated with immune system activities and inflammatory responses, while DE proteins are related to extracellular matrix production and wound repair. The upregulated genes in both phases are associated with wound repair and cell differentiation, while the downregulated genes in both phases are associated with reduced immune activities and the damage of the alveolar tissues. On this basis, we identified thirteen potential marker genes. Among them, we validated the expression changes of butyrophilin-like 9 (BTNL9) and plasmolipin (PLLP) and investigated their functional pathways in the IPF mechanism. Both genes are downregulated in the tissues of IPF patients and Bleomycin-induced mice, and co-expression analysis indicates that they have a protective effect by inhibiting extracellular matrix production and promoting wound repair in alveolar epithelial cells.
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