Identification of Genetic Signature Associated With Aging in Pulmonary Fibrosis

Yanjiao Lu; Jinkun Chen; Shanshan Wang; Zhen Tian; Yan Fan; Meijia Wang; Jianping Zhao; Kun Tang; Jungang Xie

doi:10.3389/fmed.2021.744239

Identification of Genetic Signature Associated With Aging in Pulmonary Fibrosis

Front Med (Lausanne). 2021 Oct 20:8:744239. doi: 10.3389/fmed.2021.744239. eCollection 2021.

Authors

Yanjiao Lu¹, Jinkun Chen², Shanshan Wang¹, Zhen Tian¹, Yan Fan¹, Meijia Wang¹, Jianping Zhao¹, Kun Tang^{3

4}, Jungang Xie¹

Affiliations

¹ Department of Respiratory and Critical Care Medicine, National Clinical Research Center of Respiratory Disease, Key Laboratory of Pulmonary Diseases of Health Ministry, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
² Department of Science, Western University, London, ON, Canada.
³ Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
⁴ Institute of Respiratory Diseases of Sun Yat-sen University, Guangzhou, China.

Abstract

Background: Aging is a strong risk factor and an independent prognostic factor in idiopathic pulmonary fibrosis (IPF). In this study, we aimed to conduct a comprehensive analysis based on gene expression profiles for the role of aging in pulmonary fibrosis. Method: Four datasets (GSE21411, GSE24206, GSE47460, and GSE101286) for patients with clinical IPF and one dataset for bleomycin (BLM)-induced pulmonary fibrosis (BIPF) mouse model (GSE123293) were obtained from Gene Expression Omnibus (GEO). According to different age ranges, both patients with IPF and BIPF mice were divided into young and aged groups. The differently expressed genes (DEGs) were systemically analyzed using Gene Ontology (GO) functional, Kyoto Encyclopedia of Genes and Genomes (KEGG), and hub genes analysis. Finally, we verified the role of age and core genes associated with age in vivo. Results: Via the expression profile comparisons of aged and young patients with IPF, we identified 108 aging-associated DEGs, with 21 upregulated and 87 downregulated. The DEGs were associated with "response to glucocorticoid," "response to corticosteroid," and "rhythmic process" in GO biological process (BP). For KEGG analysis, the top three significantly enriched KEGG pathways of the DEGs included "IL-17 signaling pathway," "Mineral absorption," and "HIF-1-signaling pathway." Through the comparisons of aged and young BIPF mice, a total number of 778 aging-associated DEGs were identified, with 453 genes increased and 325 genes decreased. For GO and KEGG analysis, the DEGs were enriched in extracellular matrix (ECM) and collagen metabolism. The common DEGs of patients with IPF and BIPF mice were enriched in the BP category, including "induction of bacterial agglutination," "hyaluronan biosynthetic process," and "positive regulation of heterotypic cell-cell adhesion." We confirmed that aged BIPF mice developed more serious pulmonary fibrosis. Finally, the four aging-associated core genes (Slc2a3, Fga, Hp, and Thbs1) were verified in vivo. Conclusion: This study provides new insights into the impact of aging on pulmonary fibrosis. We also identified four aging-associated core genes (Slc2a3, Fga, Hp, and Thbs1) related to the development of pulmonary fibrosis.

Keywords: aging; genetic signature; glucocorticoids; idiopathic pulmonary fibrosis; pulmonary fibrosis.