2. Academic Validation
  3. JunB orchestrates macrophage-fibroblast crosstalk in silica nanoparticle-induced pulmonary fibrosis

JunB orchestrates macrophage-fibroblast crosstalk in silica nanoparticle-induced pulmonary fibrosis

  • Ecotoxicol Environ Saf. 2025 Sep 15:303:119046. doi: 10.1016/j.ecoenv.2025.119046.
Fei Li 1,  Dandan Song 2,  Jiahua Meng 3,  Jiaqi Tian 4,  Ning Li 4,  Yongfei Zheng 5,  Zitong Zhang 4,  Xiang Yun 3,  Zengfeng Li 3,  Huiyu Sun 4,  Lin Zhang 6,  Fuhai Shen 7
Affiliations

Affiliations

  • 1 Hebei Province Key Laboratory of Occupational Health and Safety for Coal Industry, Hebei Coordinated Innovation Center of Occupational Health and Safety, School of Public Health, North China University of Science and Technology, Tangshan, Hebei 063210, China; Clinical Medical Research Center for Women and Children Diseases, Key Laboratory of Maternal & Fetal Medicine of National Health Commission of China, Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University, Jinan 250014, China.
  • 2 Clinical Medical Research Center for Women and Children Diseases, Key Laboratory of Maternal & Fetal Medicine of National Health Commission of China, Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University, Jinan 250014, China. Electronic address: songdandan1872@163.com.
  • 3 Hebei Province Key Laboratory of Occupational Health and Safety for Coal Industry, Hebei Coordinated Innovation Center of Occupational Health and Safety, School of Public Health, North China University of Science and Technology, Tangshan, Hebei 063210, China.
  • 4 Clinical Medical Research Center for Women and Children Diseases, Key Laboratory of Maternal & Fetal Medicine of National Health Commission of China, Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University, Jinan 250014, China.
  • 5 School of Public Health and Health Management, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan 250001, China.
  • 6 Clinical Medical Research Center for Women and Children Diseases, Key Laboratory of Maternal & Fetal Medicine of National Health Commission of China, Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University, Jinan 250014, China. Electronic address: zhanglin8901@163.com.
  • 7 Hebei Province Key Laboratory of Occupational Health and Safety for Coal Industry, Hebei Coordinated Innovation Center of Occupational Health and Safety, School of Public Health, North China University of Science and Technology, Tangshan, Hebei 063210, China. Electronic address: shfh600@163.com.
PMID: 40945089 DOI: 10.1016/j.ecoenv.2025.119046
Abstract

Silica nanoparticles (SiNPs) exposure represents a significant environmental and occupational hazard leading to pulmonary fibrosis; however, the underlying molecular mechanisms remain incompletely understood. This study aimed to elucidate the role of JunB signaling in SiNPs-induced pulmonary fibrosis and evaluate its therapeutic potential. A comprehensive experimental approach combining in vitro macrophage-fibroblast co-culture systems and in vivo mouse models was employed, utilizing both pharmacological inhibition and genetic silencing strategies to investigate the function of JunB. RNA Sequencing analysis was performed to identify differential gene expression patterns and potential regulatory pathways. SiNPs exposure induced macrophage Pyroptosis, subsequently promoting fibroblast transdifferentiation through JunB/AP-1 pathway activation. Notably, genetic silencing of JunB significantly attenuated the expression of transdifferentiation markers in fibroblasts exposed to pyroptotic macrophage-conditioned medium. Furthermore, pharmacological inhibition of JunB using T-5224 effectively suppressed fibroblast transdifferentiation in vitro. Importantly, intraperitoneal administration of T-5224 substantially ameliorated pulmonary fibrosis in SiNPs-exposed mice, as evidenced by reduced Collagen deposition and decreased expression of fibrotic markers. In conclusion, this study establishes JunB as a critical mediator of SiNPs-induced pulmonary fibrosis and demonstrates the therapeutic potential of JunB inhibition, which provides new insights for developing targeted treatments for lung fibrosis.

Keywords

Fibroblast transdifferentiation; JunB; Macrophage pyroptosis; Pulmonary fibrosis; Silica nanoparticles.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-12270
    99.59%, c-Fos/AP-1 Inhibitor