LGI3 prevents UVB‐induced cell death of human keratinocytes

Abstract

Leucine‐rich glioma inactivated 3 (LGI3), a member of LGI/epitempin (EPTP) family, is known to be mainly expressed in brain. However, the expression and physiological roles of LGI3 in skin cells remain unknown. In the present study, it was found for the first time that LGI3 is expressed in human skin. LGI3 was mostly expressed by normal human keratinocytes, although normal human fibroblasts and melanocytes also produced LGI3. Furthermore, ELISA and Western blot analysis showed that HaCaT human keratinocytes secreted LGI3 protein after exposure to UVB in a time‐ and dose‐dependent manner. We next investigated the possible role of LGI3 in keratinocytes. Our results showed that LGI3 protected HaCaT cells from UVB‐induced cell death. It was also found that LGI3 potently stimulates the phosphorylation of Akt, which is involved in the cell survival‐signaling cascade. Furthermore, LGI3 led to the phosphorylation of MDM2 and subsequent p53 degradation. Taken together, these data suggest that LGI3 may regulate p53 levels, and that keratinocyte‐derived LGI3 may act as a novel cytokine for skin homeostasis. This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MEST) (No. 2011‐0026587).