2. Academic Validation
  3. Gas6-Axl signal promotes indoor VOCs exposure-induced pulmonary fibrosis via pulmonary microvascular endothelial cells-fibroblasts cross-talk

Gas6-Axl signal promotes indoor VOCs exposure-induced pulmonary fibrosis via pulmonary microvascular endothelial cells-fibroblasts cross-talk

  • J Hazard Mater. 2024 Aug 5:474:134786. doi: 10.1016/j.jhazmat.2024.134786.
Qingping Liu 1,  Yong Niu 2,  Zijie Pei 3,  Yizhe Yang 1,  Yujia Xie 1,  Mengruo Wang 1,  Jingyuan Wang 1,  Mengqi Wu 1,  Jie Zheng 1,  Peihao Yang 1,  Haiyan Hao 4,  Yaxian Pang 5,  Lei Bao 6,  Yufei Dai 2,  Yujie Niu 6,  Rong Zhang 7
Affiliations

Affiliations

  • 1 Department of Toxicology, Hebei Medical University, Shijiazhuang 050017, Hebei, PR China.
  • 2 Key Laboratory of Chemical Safety and Health, National Institute for Occupational Health and Poison Control, Chinese Center for Disease Control and Prevention, Beijing 100050, China.
  • 3 Department of Thoracic Surgery, the 2nd Hospital of Hebei Medical University, Shijiazhuang 050017, PR China.
  • 4 Department of Toxicology, Hebei Medical University, Shijiazhuang 050017, Hebei, PR China; Hebei Province Center for Disease Control and Prevention, Shijiazhuang 050021, Hebei, PR China.
  • 5 Department of Toxicology, Hebei Medical University, Shijiazhuang 050017, Hebei, PR China; Hebei Key Laboratory of Environment and Human Health, Hebei Medical University, Shijiazhuang 050017, Hebei, PR China.
  • 6 Hebei Key Laboratory of Environment and Human Health, Hebei Medical University, Shijiazhuang 050017, Hebei, PR China; Occupational Health and Environmental Health, Hebei Medical University, Shijiazhuang 050017, Hebei, PR China.
  • 7 Department of Toxicology, Hebei Medical University, Shijiazhuang 050017, Hebei, PR China; Hebei Key Laboratory of Environment and Human Health, Hebei Medical University, Shijiazhuang 050017, Hebei, PR China. Electronic address: rongzhang@hebmu.edu.cn.
PMID: 38824778 DOI: 10.1016/j.jhazmat.2024.134786
Abstract

Volatile organic compounds (VOCs) as environmental pollutants were associated with respiratory diseases. Pulmonary fibrosis (PF) was characterized by an increase of extracellular matrix, leading to deterioration of lung function. The adverse effects on lung and the potential mechanism underlying VOCs induced PF had not been elucidated clearly. In this study, the indoor VOCs exposure mouse model along with an ex vivo biosensor assay was established. Based on scRNA-seq analysis, the adverse effects on lung and potential molecular mechanism were studied. Herein, the results showed that VOCs exposure from indoor decoration contributed to decreased lung function and facilitated pulmonary fibrosis in mice. Then, the whole lung cell atlas after VOCs exposure and the heterogeneity of fibroblasts were revealed. We explored the molecular interactions among various pulmonary cells, suggesting that endothelial cells contributed to fibroblasts activation in response to VOCs exposure. Mechanistically, pulmonary microvascular endothelial cells (MPVECs) secreted Gas6 after VOCs-induced PANoptosis phenotype, bound to the Axl in fibroblasts, and then activated fibroblasts. Moreover, Atf3 as the key gene negatively regulated PANoptosis phenotype to ameliorate fibrosis induced by VOCs exposure. These novel findings provided a new perspective about MPVECs could serve as the initiating factor of PF induced by VOCs exposure.

Keywords

Fibroblasts; Gas6-Axl; Pulmonary fibrosis; Pulmonary microvascular endothelial cells; Volatile organic compounds.

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