Ultraviolet B‐induced LGI3 secretion protects human keratinocytes

Abstract

Leucine-rich glioma inactivated 3 (LGI3) is known to be expressed mainly in the brain. However, the expression and physiological roles of LGI3 in skin cells remain unknown. In this study, it was found for the first time that LGI3 is expressed mostly by normal human keratinocytes. Furthermore, ELISA analysis showed that HaCaT human keratinocytes increased LGI3 secretion after exposure to ultraviolet B (UVB) in a time-and dose-dependent manner. We next investigated the possible role of LGI3 in keratinocytes. LGI3 (50 ng/ml) increased survival of HaCaT cells by 20% after UVB irradiation (150 mJ/cm 2 ). It was also found that LGI3 stimulates the phosphorylation of Akt, which is involved in the cell survival-signalling cascade.Furthermore, LGI3 led to the phosphorylation of MDM2 and subsequent p53 degradation. Taken together, the data suggest that LGI3 may regulate p53 levels and that keratinocyte-derived LGI3 may act as a novel cytokine for skin homoeostasis.Abbreviations: BSA, bovine serum albumin; ELISA, enzyme-linked immunosorbent assay; EPTP, epitempin; LGI3, leucine-rich glioma inactivated 3; PVDF, polyvinylidene fluoride; RT-PCR, reverse transcription polymerase chain reaction; UVB, ultraviolet B.

Leucine-rich glioma inactivated 3: integrative analyses support its prognostic role in glioma

“…LGI3-promoted neurite outgrowth was mediated by Akt and FAK 3. p53 and MDM2 were shown to be involved in LGI3-promoted cell survival in UVB-irradiated keratinocytes 5. β-Catenin and GSK3β mediated keratinocyte migration induced by LGI3 7.…”

“…LGI3 is also expressed in skin and adipose tissues 4,5. We showed that LGI3 secretion was induced by ultraviolet B (UVB) and promoted keratinocyte survival 5. We demonstrated that LGI3 promoted the migration of keratinocytes and melanogenesis 6,7…”

“…We reported that LGI3 regulated neuronal exocytosis and neurite outgrowth 2,3. LGI3 is also expressed in skin and adipose tissues 4,5. We showed that LGI3 secretion was induced by ultraviolet B (UVB) and promoted keratinocyte survival 5.…”

Leucine-rich glioma inactivated 3 and tumor necrosis factor-α regulate mutually through NF-κB

“…Besides the nervous system, LGI3 is expressed in diverse tissues including skin and adipose tissues [4,5]. We reported that ultraviolet B-irradiation-induced secretion of LGI3 promoted survival of human keratinocytes [5]. We also showed that LGI3 promoted keratinocyte migration and melanocyte pigmentation [6,7].…”

“…We previously showed that LGI3 played regulatory roles in neuronal exocytosis and differentiation [2,3]. Besides the nervous system, LGI3 is expressed in diverse tissues including skin and adipose tissues [4,5]. We reported that ultraviolet B-irradiation-induced secretion of LGI3 promoted survival of human keratinocytes [5].…”