Integrative omics analysis identifies biomarkers of idiopathic pulmonary fibrosis

Peiyan Zheng, Shixue Sun, Jingxian Wang, Zhangkai Jason Cheng, Kuan Cheok Lei, Mingshan Xue, Teng Zhang, Huimin Huang, Xiaohua Douglas Zhang, Baoqing Sun

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Article number66
JournalCellular and Molecular Life Sciences
Volume79
Issue number1
DOIs
StatePublished - Jan 2022

Bibliographical note

Funding Information:
This work was supported by the National Natural Science Foundation of China (Project No. 81871736), Bureau of traditional Chinese Medicine Scientific Research Project of Guangdong (Project No. 20192048), The First Affiliated Hospital Of Guangzhou Medical University (ZH201915) (funds from GMU), Guangzhou Institute of Respiratory Health Open Project (Funds provided by China Evergrande Group, Project No. 2020GIRHHMS04), the Zhongnanshan Medical Foundation of Guangdong Province (Project No: ZNSA-2021005 and Project No: ZNSA-2020001), the University of Macau (grant numbers: FHS-CRDA-029-002-2017, and MYRG2018-00071-FHS), the Science and Technology Development Fund, Macau SAR (File No. 0004/2019/AFJ and 0011/2019/AKP), and Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences (Project No. 2018PT31048). Funding for open access charge: National Natural Science Foundation of China.

Publisher Copyright:
© 2022, The Author(s), under exclusive licence to Springer Nature Switzerland AG.

Keywords

  • AEC injury
  • Immune responses
  • Multi-omics analysis
  • Myofibroblast proliferation
  • Whole-genome expression

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Cellular and Molecular Neuroscience
  • Cell Biology

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