Analysis of mitochondrial related genes in idiopathic pulmonary fibrosis

doi:10.3877/cma.j.issn.1674-6902.2024.02.002

Abstract

Abstract:

Objective

Mitochondria-related genes associated with the development of idiopathic pulmonary fibrosis were analyzed by bioinformatics methods and the pulmonary fibrosis mouse model.

Methods

Datasets were acquired from the GEO database. Analysis of differential expressed genes (DEGs) was conducted for each dataset using the GEO2R online tool. Mitochondrial-related differential expressed genes (MiRDEGs) were identified by intersecting MitoCarta3.0 database genes with DEGs. Subsequently, functional enrichment analyses and a Protein-Protein Interaction (PPI) network construction were conducted for MiRDEGs, with hub MiRDEGs identified using CytoHubba. Mouse model of bleomycin-induced pulmonary fibrosis were used to validate hub MiRDEGs.

Results

Our study identified 26 upregulated and 24 downregulated MiRDEGs linked to mitochondrial function, structure and metabolism pathways. Cytohubba identified 10 hub MiRDEGs. Immune infiltration analysis indicated abundant M₂ macrophage, M₁ macrophage, and M₀ macrophage infiltration in IPF samples. Notably, among the hub MiRDEGs, ACSL1 exhibited the most pronounced negative correlation with M₂ macrophage infiltration, while PC showed the strongest positive correlation. Animal experiments demonstrated that lower expression of FASN, PDK4, and ACSL1, and higher expression of ALDH18A1, MTHFD2, ALDH1L2, and PC in the pulmonary fibrosis mouse model compared to the control group.

Conclusion

By comprehensively exploring the genes related to mitochondria and emphasizing their impact on immune infiltration in IPF, this investigation provides insights into the molecular mechanisms underlying IPF and potential therapeutic target.

Key words: Idiopathic fibrosis of the lung, Mitochondria, Immune, Bioinformatics

Peiling Wu, Yueyan Lou, Hongyan Zhang, Dongfang Chen, Shan Xue, Lifang Zhao, Xueqing Liu, Handong Jiang. Analysis of mitochondrial related genes in idiopathic pulmonary fibrosis[J]. Chinese Journal of Lung Diseases(Electronic Edition), 2024, 17(02): 178-184.

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URL: https://zhfbjbzz.cma-cmc.com.cn/EN/10.3877/cma.j.issn.1674-6902.2024.02.002

https://zhfbjbzz.cma-cmc.com.cn/EN/Y2024/V17/I02/178

Figures/Tables 4

References 34

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MiRDEGs	引物序列
FASN	forward：5′- GGAGGTGGTGATAGCCGGTAT-3′
	reverse：5′-TGGGTAATCCATAGAGCCCAG-3′
PDK4	Forward：5′-AGGGAGGTCGAGCTGTTCTC-3′
	reverse: 5′- GGAGTGTTCACTAAGCGGTCA-3′
HMGCS2	forward：5′-GAAGAGAGCGATGCAGGAAAC-3′
	reverse：5′-GTCCACATATTGGGCTGGAAA-3′
ACSL1	forward：5′-TGCCAGAGCTGATTGACATTC-3′
	reverse: 5′-GGCATACCAGAAGGTGGTGAG-3′
ACADL	forward：5′-TCTTTTCCTCGGAGCATGACA-3′
	reverse：5′-GACCTCTCTACTCACTTCTCCAG-3′
ALDH18A1	forward：5′-GTCCAGCCCTCAGCTATTAGA-3′
	reverse：5′-CTTCAGCTCACTTCGGTGGG-3′
MTHFD2	forward：5′-AGTGCGAAATGAAGCCGTTG-3′
	reverse：5′-GACTGGCGGGATTGTCACC-3′
ALDH1L1	forward：5′-CAGGAGGTTTACTGCCAGCTA-3′
	reverse：5′-CACGTTGAGTTCTGCACCCA-3′
ALDH1L2	forward：5′-ACCAGCCGGGTTTATTTCAAA-3′
	reverse：5′-ACTCCCACTACTCGGTGGC-3′
PC	forward: 5′-CCACCTCTCCGAACCGTGACA-3′
	reverse- 5′-GAGAAGATTGGTAGGGGAGGC-3′

MiRDEGs	引物序列
FASN	forward：5′- GGAGGTGGTGATAGCCGGTAT-3′
	reverse：5′-TGGGTAATCCATAGAGCCCAG-3′
PDK4	Forward：5′-AGGGAGGTCGAGCTGTTCTC-3′
	reverse: 5′- GGAGTGTTCACTAAGCGGTCA-3′
HMGCS2	forward：5′-GAAGAGAGCGATGCAGGAAAC-3′
	reverse：5′-GTCCACATATTGGGCTGGAAA-3′
ACSL1	forward：5′-TGCCAGAGCTGATTGACATTC-3′
	reverse: 5′-GGCATACCAGAAGGTGGTGAG-3′
ACADL	forward：5′-TCTTTTCCTCGGAGCATGACA-3′
	reverse：5′-GACCTCTCTACTCACTTCTCCAG-3′
ALDH18A1	forward：5′-GTCCAGCCCTCAGCTATTAGA-3′
	reverse：5′-CTTCAGCTCACTTCGGTGGG-3′
MTHFD2	forward：5′-AGTGCGAAATGAAGCCGTTG-3′
	reverse：5′-GACTGGCGGGATTGTCACC-3′
ALDH1L1	forward：5′-CAGGAGGTTTACTGCCAGCTA-3′
	reverse：5′-CACGTTGAGTTCTGCACCCA-3′
ALDH1L2	forward：5′-ACCAGCCGGGTTTATTTCAAA-3′
	reverse：5′-ACTCCCACTACTCGGTGGC-3′
PC	forward: 5′-CCACCTCTCCGAACCGTGACA-3′
	reverse- 5′-GAGAAGATTGGTAGGGGAGGC-3′

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