Transcriptomic and metabolomic profiling reveal the p53-dependent benzeneacetic acid attenuation of silica‐induced epithelial–mesenchymal transition in human bronchial epithelial cells

Cell & Bioscience

Meiling Zhou¹  Huiji Pan¹  Ping Ding¹  Jing Jin¹  Zhao Ju¹  Ruixue Huang¹  Jianlin Shao² 

[1] Department of Occupational and Environmental Health, Xiangya School of Public Health, Central South University, 410078, Changsha, Hunan, China;Zhejiang Provincial Center for Cardiovascular Disease Prevention and Control, Zhejiang Hospital, Hangzhou, Zhejiang, China;

关键词: p53;    Silica;    EMT;   

DOI  :  10.1186/s13578-021-00545-0

来源: Springer

【 摘 要 】

BackgroundSilica exposure underlies the development of silicosis, one of the most serious occupational hazards worldwide. We aimed to explore the interaction of the silica-induced epithelial–mesenchymal transition (EMT)-related transcripts with the cellular metabolism regulated by p53. MethodsWe knocked out p53 using CRISPR/Cas9 in the human bronchial epithelial (HBE) cell line. The transcriptomic and metabolomic analyses and integrative omics were conducted using microarrays, GC–MS, and MetaboAnalyst, respectively.ResultsFifty-two mRNAs showed significantly altered expression in the HBE p53-KO cells post-silica exposure. A total of 42 metabolites were putatively involved in p53-dependent silica-mediated HBE cell dysfunction. Through integrated data analysis, we obtained five significant p53-dependent metabolic pathways including phenylalanine, glyoxylate, dicarboxylate, and linoleic acid metabolism, and the citrate cycle. Through metabolite screening, we further identified that benzeneacetic acid, a key regulation metabolite in the phenylalanine metabolic pathway, attenuated the silica-induced EMT in HBE cells in a p53-dependent manner. Interestingly, despite the extensive p53-related published literature, the clinical translation of these studies remains unsubstantial.ConclusionsOur study offers new insights into the molecular mechanisms by which epithelial cells respond to silica exposure and provide fresh perspective and direction for future clinical biomarker research and potential clinically sustainable and translatable role of p53.

【 授权许可】

CC BY