NRF2 Is a Potential Modulator of Hyperresistance to Arsenic Toxicity in Stem-Like Keratinocytes

Abstract EN

Arsenic is a well-known human carcinogen.

Stem cells are indicated to be involved in arsenic carcinogenesis and have a survival selection advantage during arsenic exposure with underlying mechanisms undefined.

In the present study, we demonstrated that CD34high-enriched cells derived from HaCaT human keratinocytes showed stem-like phenotypes.

These cells were more resistant to arsenic toxicity and had higher arsenic efflux ability than their mature compartments.

The master transcription factor in antioxidant defense, nuclear factor erythroid 2-related factor 2 (NRF2) with its downstream genes, was highly expressed in CD34high-enriched cells.

Stable knockdown of NRF2 abolished the hyperresistance to arsenic toxicity and holoclone-forming ability of CD34high-enriched cells.

Our results suggest that skin epithelial stem/progenitor cells are more resistant to arsenic toxicity than mature cells, which is associated with the high innate expression of NRF2 in skin epithelial stem/progenitor cells.