TY - JOUR
T1 - Hippo signaling pathway contributes to air pollution exposure-induced emphysema in ageing rats
AU - Laiman, Vincent
AU - Hsiao, Ta-Chih
AU - Fang, Yu-Ting
AU - Chen, You-Yin
AU - Lo, Yu-Chun
AU - Lee, Kang-Yun
AU - Chen, Tzu-Tao
AU - Chen, Kuan-Yuan
AU - Ho, Shu-Chuan
AU - Wu, Sheng-Ming
AU - Chen, Jen-Kun
AU - Heriyanto, Didik Setyo
AU - Chung, Kian Fan
AU - Ho, Kin-Fai
AU - Chuang, Kai-Jen
AU - Chang, Jer-Hwa
AU - Chuang, Hsiao-Chi
PY - 2023/6/15
Y1 - 2023/6/15
N2 - 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.
AB - 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.
KW - Air pollution
KW - Alveolar type II cell
KW - Emphysema
KW - PM(2.5)
KW - YAP/TAZ
UR - http://www.scopus.com/inward/record.url?scp=85159243993&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85159243993&partnerID=8YFLogxK
U2 - 10.1016/j.jhazmat.2023.131188
DO - 10.1016/j.jhazmat.2023.131188
M3 - Article
SN - 0304-3894
VL - 452
SP - 131188
JO - Journal of Hazardous Materials
JF - Journal of Hazardous Materials
ER -
