Integrative omics analysis identifies biomarkers of idiopathic pulmonary fibrosis

被引:11
|
作者
Zheng, Peiyan [1 ]
Sun, Shixue [1 ,2 ]
Wang, Jingxian [3 ]
Cheng, Zhangkai Jason [1 ]
Lei, Kuan Cheok [2 ]
Xue, Mingshan [1 ]
Zhang, Teng [2 ]
Huang, Huimin [1 ]
Zhang, Xiaohua Douglas [2 ]
Sun, Baoqing [1 ]
机构
[1] Guangzhou Med Univ, Natl Clin Res Ctr Resp Dis, Guangzhou Inst Resp Hlth,Affiliated Hosp 1, Dept Allergy & Clin Immunol,State Key Lab Resp Di, Guangzhou 510120, Peoples R China
[2] Univ Macau, Fac Hlth Sci, Taipa, Macao, Peoples R China
[3] Guizhou Med Univ, Key Lab Adult Stem Cell Translat Res, Natl Joint Local Engn Lab Cell Engn & Biomed Tech, Guizhou Prov Key Lab Regenerat Med,Chinese Acad M, Guiyang 550025, Guizhou, Peoples R China
基金
中国国家自然科学基金;
关键词
Multi-omics analysis; AEC injury; Whole-genome expression; Myofibroblast proliferation; Immune responses; EXPRESSION; PATHWAYS; PLASMOLIPIN; EPIGENETICS; ENDOCYTOSIS; MECHANISMS; MICRORNAS; SIGNATURE; REPAIR;
D O I
10.1007/s00018-021-04094-0
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
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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页数:21
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