2. Academic Validation
  3. CCTα and GVI iPLA2-induced aberrant phosphatidylcholine metabolism contributes to pulmonary inflammation and fibrosis

CCTα and GVI iPLA2-induced aberrant phosphatidylcholine metabolism contributes to pulmonary inflammation and fibrosis

  • Int Immunopharmacol. 2025 May 27:156:114718. doi: 10.1016/j.intimp.2025.114718.
Tao Liu 1,  Hong Jia 2,  Xinsheng Li 3,  Lijun Shi 2,  Jing Wang 2,  Meizhen Liu 4,  Hailong Liu 2,  Tao Zhang 5,  Zhenwen Zhao 6,  Xinghui Zhao 2,  Zhanzhong Zhao 7
Affiliations

Affiliations

  • 1 Laboratory of Pharmacobiology, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China; College of Animal Husbandry and Veterinary Medicine, Xinyang Agriculture and Forestry University, Xinyang 464001, China.
  • 2 Laboratory of Pharmacobiology, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China.
  • 3 College of Veterinary Medicine, Henan Agricultural University, Zhengzhou 450002, China.
  • 4 Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai 200241, China.
  • 5 Beijing Key Laboratory of Traditional Chinese Veterinary Medicine, College of Animal Science and Technology, Beijing University of Agriculture, Beijing 102206, China.
  • 6 Key Laboratory of Analytical Chemistry for Living Biosystems, Beijing Mass Spectrometry Center, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China.
  • 7 Laboratory of Pharmacobiology, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China. Electronic address: zhaozhanzhong@caas.cn.
PMID: 40286783 DOI: 10.1016/j.intimp.2025.114718
Abstract

To date, no comprehensive profiling of phosphatidylcholine (PC) and lysophosphatidylcholine (LPC) with pulmonary inflammation and fibrosis has been published. Our study aimed to analyze PC and LPC metabolism with the development and persistence of pulmonary inflammation and the progression to fibrosis; and their relationship. Mice and cell models exposed to bleomycin and/or transforming growth factor-β1 (TGF-β1) were developed; and porcine surrogates for pulmonary fibrosis were included. Histopathological, immunofluorescence and immunohistochemical staining, transmission electron microscopy, colorimetric, activity and immune complex (IC) assay, lipidomics analysis; and pharmacological intervention assay were used to analyze PC and LPC profile, pulmonary fibrosis and their relationship. Current evidence suggests that 16:0 20:5 PC is a conserved biomarker; and 16:0 18:1 PC, 16:0 18:2 PC; and 16:0 LPC are the potential targets for this disease. Specifically, 16:0 18:1 PC accumulation and exogenous treatment affected lung cell recruitment, migration, transformation, cross-talk, survival/death; and enhanced profibrotic factor release, IC and extracellular matrix (ECM) deposition, where CTP:phosphocholine cytidylyltransferase α (CCTα) and group VI CA2+-independent Phospholipase A2 (GVI iPLA2) play an important role, particularly in lung and spleen neutrophils, macrophages, and T lymphocytes. Overall, these results provide new insights into how the dysregulated PC metabolism, particularly for 16:0 18:1 PC, affects the development and persistence of lung inflammation and the progression to fibrosis, and thus may facilitate the discovery of biomarkers and targets for this disease.

Keywords

CCTα; Fibrosis; GVI iPLA2; Inflammation; Lung; PC.

Figures
Products