Transcriptomic profiling of human corneal epithelial cells exposed to airborne fine particulate matter (PM2.5)

• Published in: The ocular surface 2020-10, Vol.18 (4), p.554-564
• Main Authors: Lyu, Danni, Chen, Zhijian, Almansoob, Siham, Chen, Hui, Ye, Yang, Song, Fan, Zhang, Lifang, Qin, Zhenwei, Tang, Qiaomei, Yin, Houfa, Xu, Wen, Yao, Ke, Fu, Qiuli
• Format: Article
• Language: English
• Subjects: Animals; Autophagy; Cornea; Epithelial Cells; Human corneal epithelial cell; Humans; PAI-2; Particulate Matter - toxicity; PM2.5; Rat cornea; Rats; Transcriptome
• ISSN: 1542-0124; 1937-5913
• DOI: 10.1016/j.jtos.2020.06.003

To explore the molecular mechanisms of PM2.5-induced dysfunction in human corneal epithelial cells (HCECs) and the potential role of the plasminogen activator inhibitor type-2 (PAI-2) in PM2.5-induced autophagy in vitro and in vivo. RNA-Seq was performed to identify the differentially expressed genes (DEGs) in PM2.5-exposed HCECs compared to unexposed condition, followed by validation via real-time PCR (qRT-PCR). Corneal fluorescein staining and tear secretion were assessed in the PM2.5-exposed rat model. The expression of PAI-2 and autophagy-related markers were examined via immunoblotting, immunofluorescence staining and/or qRT-PCR in PM2.5-exposed or unexposed HCECs and rat corneas. PAI-2-knockdown HCECs were generated to study PAI-2's role in the PM2.5-induced autophagy in HCECs. A total of 434 DEGs—240 up-regulated and 194 down-regulated—were identified in PM2.5-exposed HCECs rather than unexposed HCECs. The expression of a few genes related to proliferation, inflammation, and aryl hydrocarbon stimulation were significantly altered by PM2.5 exposure. PAI-2 expression was up-regulated in PM2.5-exposed HCECs, sharing a similar fluctuation trend with autophagy-related markers LC3B II and BECN1 according to various exposure periods. Moreover, PAI-2 knockdown significantly suppressed the expression of LC3B and BECN1 in PM2.5-exposed HCECs. The corneal fluorescein staining was enhanced and tear secretion was significantly reduced in PM2.5-exposed rat eyes. PAI-2 expression was also increased in PM2.5-exposed rat corneas, together with the up-regulation of several autophagy-related markers. The present study identified the altered expression of hundreds of genes in PM2.5-exposed HCECs, which suggests the importance of PM2.5 for cornea health. The involvement of PAI-2 was discovered in the PM2.5-induced autophagy in HCECs as well as likely in rat corneas, which implied that PAI-2 may become a potential target of clinical treatment of PM2.5-associated ocular surface diseases. [Display omitted] •PM2.5 alters proliferation, inflammation, and response to aryl hydrocarbon in vitro.•PM2.5 exposure causes corneal injury and decreased tear secretion in rat model.•Autophagy plays a role in PM2.5-induced corneal dysfunction in vitro and in vivo.•PAI-2 participates in PM2.5-induced corneal autophagy in vitro and likely in vivo.