Transcriptomics reveals key regulatory pathways and genes associated with skin diseases induced by face paint usage.

The use of face paint cosmetics can cause skin diseases in opera performers due to the presence of heavy metals and other toxic ingredients in the cosmetics. However, the underlying molecular mechanism for these diseases remains unknown. Here we examined the transcriptome gene profile of human skin keratinocytes exposed to artificial sweat extracts of face paints, and identified the key regulatory pathways and genes, using RNA sequencing technique. Bioinformatics analyses suggested that the face paint exposure induced the differentially expression of 1531 genes and enriched inflammation-relevant TNF and IL-17 signaling pathways after just 4 h of exposure. Inflammation-relevant genes CREB3L3, FOS, FOSB, JUN, TNF, and NFKBIA were identified as the potential regulatory genes, and SOCS3 capable to prevent inflammation-induced carcinogenesis as the hub-bottleneck gene. Long-term exposure (24 h) could exacerbate inflammation, accompanied by interference in cellular metabolism pathways, and the potential regulatory genes (ATP1A1, ATP1B1, ATP1B2, FXYD2, IL6, and TNF) and hub-bottleneck genes (JUNB and TNFAIP3) were all related to inflammation induction and other adverse responses. We proposed that the exposure to face paint might cause the inflammatory factors TNF and IL-17, which are encoded by the genes TNF and IL17, to bind to receptors and activate TNF and IL-17 signaling pathways, leading to the expression of cell proliferation factors (CREB and AP-1) and proinflammatory mediators including transcription factors (FOS, JUN, and JUNB), inflammatory factors (TNF-α and IL6), and intracellular signaling factors (TNFAIP3). This finally resulted in cell inflammation, apoptosis, and other skin diseases. TNF was identified as the key regulator and connector in all the enriched signaling pathways. Our study provides the first insights into the cytotoxicity mechanism of face paints to skin cells and highlights the need for stricter regulations in face paint safety.