Role and mechanism of WNT5A in benzo(a)pyrene-induced acute lung injury and lung function decline.

Lieyang Fan, Bin Wang, Jixuan Ma, Zi Ye, Xiuquan Nie, Man Cheng, Yujia Xie, Pei Gu, Yingdie Zhang, Xiaojie You, Yun Zhou, Weihong Chen

Journal of hazardous materials 2023 Oct 15

filter terms:

Benzo(a)pyrene was sparsely studied for its early respiratory impairment. The non-canonical ligand WNT5A play a role in pneumonopathy, while its function during benzo(a)pyrene-induced adverse effects were largely unexplored. Individual benzo(a)pyrene, plasma WNT5A, and spirometry 24-hour change for 87 residents from Wuhan-Zhuhai cohort were determined to analyze potential role of WNT5A in benzo(a)pyrene-induced lung function alternation. Normal bronchial epithelial cell lines were employed to verify the role of WNT5A after benzo(a)pyrene treatment. RNA sequencing was adopted to screen for benzo(a)pyrene-related circulating microRNAs and differentially expressed microRNAs between benzo(a)pyrene-induced cells and controls. The most potent microRNA was selected for functional experiments and target gene validation, and their mechanistic link with WNT5A-mediated non-canonical Wnt signaling was characterized through rescue assays. We found significant associations between increased benzo(a)pyrene and reduced 24-hour changes of FEF50% and FEF75%, as well as increased WNT5A. The benzo(a)pyrene-induced inflammation and epithelial-mesenchymal transition in BEAS-2B and 16HBE cells were attenuated by WNT5A silencing. hsa-miR-122-5p was significantly and positively associated with benzo(a)pyrene and elevated after benzo(a)pyrene induction, and exerted its effect by downregulating target gene TP53. Functionally, WNT5A participates in benzo(a)pyrene-induced lung epithelial injury via non-canonical Wnt signaling modulated by hsa-miR-122-5p/TP53 axis, showing great potential as a preventive and therapeutic target. Copyright © 2023. Published by Elsevier B.V.

Citation

Lieyang Fan, Bin Wang, Jixuan Ma, Zi Ye, Xiuquan Nie, Man Cheng, Yujia Xie, Pei Gu, Yingdie Zhang, Xiaojie You, Yun Zhou, Weihong Chen. Role and mechanism of WNT5A in benzo(a)pyrene-induced acute lung injury and lung function decline. Journal of hazardous materials. 2023 Oct 15;460:132391