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Article

PM2.5 Induces Early Epithelial Mesenchymal Transition in Human Proximal Tubular Epithelial Cells through Activation of IL-6/STAT3 Pathway

by 1,2,3, 2,4,†, 3,5,6,7 and 1,8,*,†
1
Division of Pediatric Immunology and Nephrology, Department of Pediatrics, Taipei Veterans General Hospital, Taipei 112201, Taiwan
2
Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei 112304, Taiwan
3
College of Science and Engineering, Fu Jen Catholic University, New Taipei 242062, Taiwan
4
Department of Pediatrics, Taipei City Hospital, Zhongxing Branch, Taipei 10341, Taiwan
5
Division of Nephrology, Department of Medicine, Taipei City Hospital, ZhongXing Branch, Taipei 10341, Taiwan
6
Faculty of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Hsinchu 300093, Taiwan
7
Institute of Food Safety and Health Risk Assessment, National Yang Ming Chiao Tung University, Hsinchu 300093, Taiwan
8
Institute of Emergency and Critical Care Medicine, National Yang Ming Chiao Tung University, Taipei 112304, Taiwan
*
Author to whom correspondence should be addressed.
These authors contributed equally.
Academic Editor: Andrea Huwiler
Int. J. Mol. Sci. 2021, 22(23), 12734; https://doi.org/10.3390/ijms222312734
Received: 3 November 2021 / Accepted: 23 November 2021 / Published: 25 November 2021
(This article belongs to the Section Biochemistry)
Particulate matter exposure has been known as a potential risk for the global burden of disease, such as respiratory and cardiovascular diseases. Accumulating evidence suggests that PM2.5 (particulate matter with a diameter less than 2.5 μm) is associated with increased risk of kidney disease, but the mechanisms underlying the renal injury caused by PM2.5 remain to be elucidated. This study investigated the effects of PM2.5 on human proximal tubular epithelial (HK-2) cells by monolayer and 3D spheroid cultures and explored the potential mechanisms. The typical morphology of HK-2 cells showed epithelial–mesenchymal transition (EMT), resulting in reduced adhesion and enhanced migration after PM2.5 exposure, and was accompanied by decreased E-cadherin expression and increased vimentin and α-SMA expressions. Exposure to PM2.5 in the HK-2 cells could lead to an increase in interleukin-6 (IL-6) levels and cause the activation of signal transducer and activator of transcription 3 (STAT3), which is involved in EMT features of HK-2 cells. Furthermore, blocking IL-6/STAT3 signaling by an IL-6 neutralizing antibody or STAT3 inhibitor was sufficient to reverse PM2.5-induced EMT characteristics of the HK-2 cells. Our study suggests that PM2.5 could induce early renal tubule cell injury, contributing to EMT change, and the induction of IL-6/STAT3 pathway may play an important role in this process. View Full-Text
Keywords: PM2.5; interleukin-6; epithelial–mesenchymal transition; STAT3 PM2.5; interleukin-6; epithelial–mesenchymal transition; STAT3
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MDPI and ACS Style

Lin, C.-H.; Wan, C.; Liu, W.-S.; Wang, H.-H. PM2.5 Induces Early Epithelial Mesenchymal Transition in Human Proximal Tubular Epithelial Cells through Activation of IL-6/STAT3 Pathway. Int. J. Mol. Sci. 2021, 22, 12734. https://doi.org/10.3390/ijms222312734

AMA Style

Lin C-H, Wan C, Liu W-S, Wang H-H. PM2.5 Induces Early Epithelial Mesenchymal Transition in Human Proximal Tubular Epithelial Cells through Activation of IL-6/STAT3 Pathway. International Journal of Molecular Sciences. 2021; 22(23):12734. https://doi.org/10.3390/ijms222312734

Chicago/Turabian Style

Lin, Chien-Hung, Chuan Wan, Wen-Sheng Liu, and Hsin-Hui Wang. 2021. "PM2.5 Induces Early Epithelial Mesenchymal Transition in Human Proximal Tubular Epithelial Cells through Activation of IL-6/STAT3 Pathway" International Journal of Molecular Sciences 22, no. 23: 12734. https://doi.org/10.3390/ijms222312734

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