Biomol Ther.  2023 Nov;31(6):648-654. 10.4062/biomolther.2023.112.

Aquaporin-3 Downregulation in Vitiligo Keratinocytes Increases Oxidative Stress of Melanocytes

• Kim NH
• Kim HJ
• Lee AY

• KMID: 2547497
• DOI: http://doi.org/10.4062/biomolther.2023.112

Abstract

Oxidative stress-induced melanocyte apoptosis is linked to the immune system and plays a critical role in the pathogenesis of vitiligo. Aquaporin-3 (AQP3), which is downregulated in vitiligo keratinocytes, regulates intracellular H₂O₂ accumulation. However, the role of AQP3 in oxidative stress is uncertain in vitiligo. This study investigated the effect of downregulated AQP3 on oxidative stress in vitiligo using lesional and non-lesional skin specimen sets from vitiligo patients and primary cultured adult normal human epidermal keratinocytes, with or without downregulation and overexpression of AQP3 in the presence or absence of H₂O₂ treatment. The levels of nuclear factor E2-related factor 2 (NRF2) and/or its main target, NAD(P)H quinone dehydrogenase 1 (NQO-1), were lower in the lesional keratinocytes and cultured keratinocytes with AQP3 knockdown, but were increased in keratinocytes upon AQP3 overexpression. Ratios of NRF2 nuclear translocation and NQO-1 expression levels were further reduced in AQP3-knockdown keratinocytes following H₂O₂ treatment. The conditioned media from AQP3-knockdown keratinocytes treated with H₂O₂ contained higher concentrations of reactive oxygen species (ROS). Moreover, the number of viable melanocytes was reduced when the conditioned media were added to the culture media. Overall, AQP3 downregulation in the keratinocytes of patients with vitiligo can induce oxidative stress in neighboring melanocytes, leading to melanocyte death.

Keyword

AQP3; NRF2; NQO-1; Oxidative stress; Melanocyte apoptosis