TY - JOUR
T1 - Zinc Oxide Nanoparticles Promote YAP/TAZ Nuclear Localization in Alveolar Epithelial Type II Cells
AU - Laiman, Vincent
AU - Heriyanto, Didik Setyo
AU - Lee, Yueh Lun
AU - Lai, Ching Huang
AU - Pan, Chih Hong
AU - Chen, Wei Liang
AU - Wang, Chung Ching
AU - Chuang, Kai Jen
AU - Chang, Jer Hwa
AU - Chuang, Hsiao Chi
N1 - Funding Information:
Funding: This study was funded by the Ministry of Science and Technology of Taiwan (MOST 109-2314-B-038-093-MY3).
Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2022/2
Y1 - 2022/2
N2 - 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 multiplepath 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 βcatenin, 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.
AB - 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 multiplepath 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 βcatenin, 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.
KW - Hippo pathway
KW - Lung deposition
KW - Nanoparticle
KW - Physicochemistry
KW - Senescence
KW - Welding fumes
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U2 - 10.3390/atmos13020334
DO - 10.3390/atmos13020334
M3 - Article
AN - SCOPUS:85125014567
SN - 2073-4433
VL - 13
JO - ATMOSPHERE
JF - ATMOSPHERE
IS - 2
M1 - 334
ER -