UVR Promotes Keratinocyte Phagocytosis and Skin Pigmentation Through TRPA1 Channels

Abstract

Ultraviolet radiation (UVR) enhances skin pigmentation, which involves the production of melanin by melanocytes and subsequent transfer to keratinocytes. In the epidermis, keratinocyte phagocytosis plays a pivotal role in the process of melanosome transfer to protect DNA of epidermal cells against damage from UVR. Previous research suggested that transient receptor potential channels ankyrin 1 (TRPA1) was required for UVR-induced early melanin synthesis in melanocytes. Currently, there is no evidence that supports the detailed mechanism of TRPA1 for UVR-induced phagocytosis by keratinocytes. Here, we investigated the effect and the possible mechanisms of TRPA1 on keratinocyte phagocytosis and skin pigmentation after UVR exposure. Methods: Flow cytometry was applied to investigate the effect of TRPA1 on intracellular calcium concentration ([Ca 2+ ] ic ) and fluorescent microspheres uptake was carried out to analyze phagocytosis in HaCaT cells (human immortalized keratinocytes). Western blotting was applied to measure the protein expression of calcium/calmodulin-dependent protein kinase II (CaMKII), phosphorylated CaMKII and β-catenin after UVA/UVB exposure. Masson-Fontana staining was applied to observe the effect of XAV-939 (decreasing the expression of β-catenin) on UVB-induced skin pigmentation in guinea pigs. Results: TRPA1 channels activated by UVR increased the [ca 2+ ] ic and phosphorylation of CaMKII in HaCaT cells. The UVR-induced phagocytosis was regulated by TRPA1 in HaCaT cells. TRPA1 promoted the protein expression of β-catenin after UVR exposure in HaCaT cells. XAV-939, inhibiting β-catenin expression, decreased the UVB-induced skin pigmentation on in vivo guinea pig models. Conclusion: Taken together, TRPA1 activated by UVR led to the increase of intracellular calcium, which promoted the phosphorylation of CaMKII, enhancing keratinocyte phagocytosis. Moreover, TRPA1 regulated the protein expression of β-catenin to exert a lightening effect on skin pigmentation. Our findings suggest that TRPA1 may be a potential therapeutic target for UVR-induced skin pigmentary diseases.

Opsin 3 mediates UVA-induced keratinocyte supranuclear melanin cap formation

“…Our study and other teams’ research showed that ultraviolet or blue light can drive the mobilization of calcium stored in melanocytes and fibroblasts through OPN3 21 , 26 . Further studies found that UVA led to the intracellular calcium via transient receptor potential channels ankyrin 1 and promoted the phosphorylation of CaMKII in HaCaT 36 . However, whether the calcium signaling pathway is involved in melanin cap formation is unknown.…”

Photoprotective Effects of Epigallocatechin Gallate on Ultraviolet-Induced Zebrafish and Human Skin Fibroblasts Cells

“…The overexposure of normal skin to solar UVR may give rise to short-term reactions such as erythema and atypical pigmentation, and long-term responses increasing a risk factor of developing photoaging and skin disorders [ 20 ]. Chronological aging in human skin, like photoaging is a cumulative biological process, which leads to the evolutionary modification of structural and functional features [ 21 ].…”