We investigated Hippo signaling pathway components in emphysema development of air pollution-exposed ageing rats. Male 1.5-year-old Fischer 344 ageing rats were exposed to low-level traffic-related air pollution via whole-body exposure for 3 months with/without high-efficiency particulate air (HEPA) filtration (gaseous vs. gaseous and particulate matter with aerodynamic diameter of ≤2.5 µm (PM2.5)). MLE-12 type II alveolar epithelial cells (AECII) were exposed to 0, 1, and 50 μg/mL diesel exhaust particles (DEPs). Human lung sections from non-smokers, smokers, and chronic obstructive pulmonary disease (COPD) subjects were used for confirmation. RNA-sequencing revealed that DEP decreased lung development-related genes. Air pollution resulted in 52.05% PM2.5 being deposited in alveolar region, with emphysema and increased airway thickness by micro-computed tomography (CT) and histological sections. Air pollution decreased phosphorylated (p)YAP/YAP ratio, while increasing pTAZ/TAZ ratio in DEP-exposed MLE-12 AECII and in rat SPC-positive (SPC+) AECII. Air pollution decreased E-cadherin and ⍺-catenin, while increasing SPC, LGALS3, and T1⍺ expressions. Air pollution decreased lung pSIRT1/SIRT1 ratio. In human subjects, smokers SPC+ AECII showed decreased pYAP/YAP ratio. In conclusion, air pollution can cause emphysema by Hippo pathway dysregulation with decreased cell adherens junctions, increased cell differentiation, and senescence. Hippo pathway dysregulation may also cause emphysema development in smokers.

Graphical abstract.
Original languageEnglish
Pages (from-to)131188
Number of pages1
JournalJournal of Hazardous Materials
Publication statusPublished - Jun 15 2023


  • Air pollution
  • Alveolar type II cell
  • Emphysema
  • PM(2.5)

ASJC Scopus subject areas

  • Pollution
  • Waste Management and Disposal
  • Health, Toxicology and Mutagenesis
  • Environmental Engineering
  • Environmental Chemistry


Dive into the research topics of 'Hippo signaling pathway contributes to air pollution exposure-induced emphysema in ageing rats'. Together they form a unique fingerprint.

Cite this