Zinc Oxide Nanoparticles Promote YAP/TAZ Nuclear Localization in Alveolar Epithelial Type II Cells

We investigated roles of Hippo signaling pathway components in alveolar type II cells (AECII) after zinc oxide nanoparticle (ZnONP) exposure. ZnONPs physicochemistry was characterized using field emission-scanning electron microscopy (FE-SEM) and energy-dispersive X-ray (EDX) microanalysis. ZnONP de...

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Main Authors: Vincent Laiman, Didik Setyo Heriyanto, Yueh-Lun Lee, Ching-Huang Lai, Chih-Hong Pan, Wei-Liang Chen, Chung-Ching Wang, Kai-Jen Chuang, Jer-Hwa Chang, Hsiao-Chi Chuang
Format: Article
Language:English
Published: MDPI AG 2022-02-01
Series:Atmosphere
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Online Access:https://www.mdpi.com/2073-4433/13/2/334
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author Vincent Laiman
Didik Setyo Heriyanto
Yueh-Lun Lee
Ching-Huang Lai
Chih-Hong Pan
Wei-Liang Chen
Chung-Ching Wang
Kai-Jen Chuang
Jer-Hwa Chang
Hsiao-Chi Chuang
author_facet Vincent Laiman
Didik Setyo Heriyanto
Yueh-Lun Lee
Ching-Huang Lai
Chih-Hong Pan
Wei-Liang Chen
Chung-Ching Wang
Kai-Jen Chuang
Jer-Hwa Chang
Hsiao-Chi Chuang
author_sort Vincent Laiman
collection DOAJ
description We investigated roles of Hippo signaling pathway components in alveolar type II cells (AECII) after zinc oxide nanoparticle (ZnONP) exposure. ZnONPs physicochemistry was characterized using field emission-scanning electron microscopy (FE-SEM) and energy-dispersive X-ray (EDX) microanalysis. ZnONP deposition in human respiratory tract was estimated using multiple-path particle dosimetry (MPPD) model. MLE-12 AECII were cultured and exposed to 0, 1, and 5 μg/mL of ZnONPs for 24 h. Western blots were used to investigate signaling pathways associated with Yes-associated protein (YAP)/transcriptional co-activator with PDZ-binding motif (TAZ), cell adherens junctions, differentiation, and senescence. ZnONPs morphology was irregular, with Zn and O identified. Approximately 72% of inhaled ZnONPs were deposited in lungs, with 26% being deposited in alveolar regions. ZnONP exposure increased nuclear YAP expression and decreased cytoplasmic YAP expression by AECII. Adherens junction proteins, E-cadherin, α-catenin, and β-catenin, on AECII decreased after ZnONP exposure. ZnONP exposure of AECII increased alveolar type I (AECI) transition protein, LGALS3, and the AECI protein, T1α, while decreasing AECII SPC expression. ZnONP exposure induced Sirt1 and p53 senescence proteins by AECII. Our findings showed that inhalable ZnONPs can deposit in alveoli, which promotes YAP nuclear localization in AECII, resulting in decrease tight junctions, cell differentiation, and cell senescence.
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spelling doaj.art-775b1a2a5e7841af954fa1c809e3da3e2023-11-23T18:46:00ZengMDPI AGAtmosphere2073-44332022-02-0113233410.3390/atmos13020334Zinc Oxide Nanoparticles Promote YAP/TAZ Nuclear Localization in Alveolar Epithelial Type II CellsVincent Laiman0Didik Setyo Heriyanto1Yueh-Lun Lee2Ching-Huang Lai3Chih-Hong Pan4Wei-Liang Chen5Chung-Ching Wang6Kai-Jen Chuang7Jer-Hwa Chang8Hsiao-Chi Chuang9International PhD Program in Medicine, College of Medicine, Taipei Medical University, Taipei 11031, TaiwanDepartment of Anatomical Pathology, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada—Dr. Sardjito Hospital, Yogyakarta 55281, IndonesiaDepartment of Microbiology and Immunology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, TaiwanSchool of Public Health, National Defense Medical Center, Taipei 11490, TaiwanSchool of Public Health, National Defense Medical Center, Taipei 11490, TaiwanDepartment of Family and Community Medicine, Division of Family Medicine, Tri-Service General Hospital, Taipei 11490, TaiwanDepartment of Family and Community Medicine, Division of Family Medicine, Tri-Service General Hospital, Taipei 11490, TaiwanSchool of Public Health, College of Public Health, Taipei Medical University, Taipei 11031, TaiwanSchool of Respiratory Therapy, College of Medicine, Taipei Medical University, Taipei 11031, TaiwanSchool of Respiratory Therapy, College of Medicine, Taipei Medical University, Taipei 11031, TaiwanWe investigated roles of Hippo signaling pathway components in alveolar type II cells (AECII) after zinc oxide nanoparticle (ZnONP) exposure. ZnONPs physicochemistry was characterized using field emission-scanning electron microscopy (FE-SEM) and energy-dispersive X-ray (EDX) microanalysis. ZnONP deposition in human respiratory tract was estimated using multiple-path particle dosimetry (MPPD) model. MLE-12 AECII were cultured and exposed to 0, 1, and 5 μg/mL of ZnONPs for 24 h. Western blots were used to investigate signaling pathways associated with Yes-associated protein (YAP)/transcriptional co-activator with PDZ-binding motif (TAZ), cell adherens junctions, differentiation, and senescence. ZnONPs morphology was irregular, with Zn and O identified. Approximately 72% of inhaled ZnONPs were deposited in lungs, with 26% being deposited in alveolar regions. ZnONP exposure increased nuclear YAP expression and decreased cytoplasmic YAP expression by AECII. Adherens junction proteins, E-cadherin, α-catenin, and β-catenin, on AECII decreased after ZnONP exposure. ZnONP exposure of AECII increased alveolar type I (AECI) transition protein, LGALS3, and the AECI protein, T1α, while decreasing AECII SPC expression. ZnONP exposure induced Sirt1 and p53 senescence proteins by AECII. Our findings showed that inhalable ZnONPs can deposit in alveoli, which promotes YAP nuclear localization in AECII, resulting in decrease tight junctions, cell differentiation, and cell senescence.https://www.mdpi.com/2073-4433/13/2/334Hippo pathwaylung depositionnanoparticlephysicochemistrysenescencewelding fumes
spellingShingle Vincent Laiman
Didik Setyo Heriyanto
Yueh-Lun Lee
Ching-Huang Lai
Chih-Hong Pan
Wei-Liang Chen
Chung-Ching Wang
Kai-Jen Chuang
Jer-Hwa Chang
Hsiao-Chi Chuang
Zinc Oxide Nanoparticles Promote YAP/TAZ Nuclear Localization in Alveolar Epithelial Type II Cells
Atmosphere
Hippo pathway
lung deposition
nanoparticle
physicochemistry
senescence
welding fumes
title Zinc Oxide Nanoparticles Promote YAP/TAZ Nuclear Localization in Alveolar Epithelial Type II Cells
title_full Zinc Oxide Nanoparticles Promote YAP/TAZ Nuclear Localization in Alveolar Epithelial Type II Cells
title_fullStr Zinc Oxide Nanoparticles Promote YAP/TAZ Nuclear Localization in Alveolar Epithelial Type II Cells
title_full_unstemmed Zinc Oxide Nanoparticles Promote YAP/TAZ Nuclear Localization in Alveolar Epithelial Type II Cells
title_short Zinc Oxide Nanoparticles Promote YAP/TAZ Nuclear Localization in Alveolar Epithelial Type II Cells
title_sort zinc oxide nanoparticles promote yap taz nuclear localization in alveolar epithelial type ii cells
topic Hippo pathway
lung deposition
nanoparticle
physicochemistry
senescence
welding fumes
url https://www.mdpi.com/2073-4433/13/2/334
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