Clinical, Cosmetic and Investigational Dermatology (Jun 2022)
UVR Promotes Keratinocyte Phagocytosis and Skin Pigmentation Through TRPA1 Channels
Abstract
Ying Liu,1,* Zhou Li,1,* Wei Wu,1,* Yupeng Wang,1 Guangming Zhao,1 Yuejian Liu,2 Jing Liu,3 Zhiqi Song1 1Department of Dermatology, First Affiliated Hospital of Dalian Medical University, Dalian, People’s Republic of China; 2Central Laboratory, First Affiliated Hospital of Dalian Medical University, Dalian, People’s Republic of China; 3Stem Cell Clinical Research Center, First Affiliated Hospital of Dalian Medical University, Dalian, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhiqi Song, Department of Dermatology, First Affiliated Hospital of Dalian Medical University, 222 Zhongshan Road, Dalian, 116011, People’s Republic of China, Email [email protected]: 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 ([Ca2+]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 [ca2+]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.Keywords: transient receptor potential arkyin 1, ultraviolet radiation, phagocytosis, skin pigmentation, CaMKII, β-catenin
