Evolutionally conserved Wnt, Hedgehog (Hh) and Notch morphogen pathways play essential roles in the development, homeostasis and pathogenesis of multicellular organisms. Nevertheless, mechanisms that intracellularly coordinate these signal inputs remain poorly understood. Here we found that parafibromin, a component of the PAF complex, competitively interacts with β-catenin and Gli1, thereby potentiating transactivation of Wnt- and Hh-target genes in a mutually exclusive manner. Parafibromin also binds to the Notch intracellular domain (NICD), enabling concerted activation of Wnt- and Notch-target genes. The transcriptional platform function of parafibromin is potentiated by tyrosine dephosphorylation, mediated by SHP2 phosphatase, while it is attenuated by tyrosine phosphorylation, mediated by PTK6 kinase. Consequently, acute loss of parafibromin in mice disorganizes the normal epithelial architecture of the intestine, which requires coordinated activation/inactivation of Wnt, Hh and/or Notch signalling. Parafibromin integrates and converts signals conveyed by these morphogen pathways into appropriate transcriptional outputs in a tyrosine phosphorylation/dephosphorylation-regulated manner.

The effects of blue light on human body have attracted attention. The human skin in contact with the outside environment is often exposed to blue light, and the effects of this exposure remain to be fully determined. Therefore, in this study, we investigated the effect of blue light, at the intensity typically found in sunlight, on lipids in the skin from an oxidation perspective. Peroxide value (POV) and ultraweak photon emission (UPE) measurements were conducted to evaluate lipid oxidation. Our results confirmed that blue light irradiation induced lipid oxidation, similar to ultraviolet A (UVA) irradiation. Also, the effects of various reagents on the blue light-induced UPE were evaluated; however, the results differed from those of the DPPH radical-scavenging ability. We speculated that this is due to the difference in the evaluation principle; nevertheless, among reagents, hypotaurine not only showed a high antioxidant effect but was also more effective against blue light-induced oxidation than UVA. Based on the difference in the antioxidant effect of the lipid sample in this study, the oxidation reaction induced by blue light may be different from the UVA-induced reaction. Our study provides new insights into the effects of blue light on lipids in the human skin, thereby promoting research regarding photooxidation. Graphical abstract

ThehumanskinisusuallyexposedtoultravioletA(UVA)inthesunlightandexperiencesoxidativestressassociatedwithskindisordersandaging.Althoughoxidative stresscausedbyUVAexposureisassumedtobedependentonskincolour,fewstudieshavedemonstratedthisdependency.Weinvestigatedtheeffectsofskincolouron UVA-inducedoxidativestressusingultraweakphotonemission(UPE)generatedfrom the skin during oxidation processes. The UPE intensities of skin samples were detectedusingaphotomultipliertubeeverysecondwithoutanylabelling.Weirradiated skintissueofdifferentcolourswithUVAandmeasuredUPEovertime.UVA-induced UPEcouldbedetectedfromimmediatelyafterirradiationto2hafterirradiation,indicatingpersistentoxidativestress.Skinlightness(L*)positivelycorrelateswithUPE intensity.Lighter-colouredskinexhibitedmoreUVA-inducedUPE,indicatinghigher oxidative stress. Additionally, oxidative stress persisted significantly more in lighter skincomparedwithdarkerskin.SkintissuesexhibitedpigmentdarkeningafterUVA irradiation.Ourresultssuggestthatskinlightnessaffectsoxidativestressinducedby UVirradiation.Ourstudydemonstratedtherelationshipbetweenskinlightnessand UVA-inducedoxidativestressforthefirsttimeandoffersnewphotodermatological insightsintothehumanskin.