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Dynamic regulation of retinoic acid-binding proteins in developing, adult and neoplastic skin reveals roles for β-catenin and Notch signalling

机译:发育中,成年和赘生性皮肤中视黄酸结合蛋白的动态调节揭示了β-catenin和Notch信号的作用

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Retinoicacid(RA)signallingisessentialforepidermaldifferentiation;however,themechanismsbywhichitactsarelargelyunexplored.PartitioningofRAbetweendifferentnuclearreceptorsisregulatedbyRA-bindingproteins.WeshowthatcellularRA-bindingproteinsCRABP1andCRABP2andthefattyacid-bindingproteinFABP5aredynamicallyexpressedduringskindevelopmentandinadulttissue.CRABP1isexpressedinembryonicdermisandinthestromaofskintumours,butconfinedtothehairfollicledermalpapillainnormalpostnatalskin.CRABP2andFABP5areexpressedinthedifferentiatingcellsofsebaceousgland,interfollicularepidermisandhairfollicles,withFABP5beingaprominentmarkerofsebaceousglandsandanagenfolliclebulbs.AllthreeproteinsareupregulatedinresponsetoRAtreatmentorNotchactivationandarenegativelyregulatedbyWnt/β-cateninsignalling.Ectopicfolliclesinducedbyβ-cateninarisefromareasofthesebaceousglandthathavelostCRABP2andFABP5;conversely,inhibitionofhairfollicleformationbyN-terminallytruncatedLef1resultsinupregulationofCRABP2andFABP5.OurfindingsdemonstratethatthereisdynamicregulationofRAsignallingindifferentregionsoftheskinandprovideevidenceforinteractionsbetweentheRA,β-cateninandNotchpathways./p/div
机译:维甲酸(RA)signallingisessentialforepidermaldifferentiation;然而,themechanismsbywhichitactsarelargelyunexplored.PartitioningofRAbetweendifferentnuclearreceptorsisregulatedbyRA-bindingproteins.WeshowthatcellularRA-bindingproteinsCRABP1andCRABP2andthefattyacid-bindingproteinFABP5aredynamicallyexpressedduringskindevelopmentandinadulttissue.CRABP1isexpressedinembryonicdermisandinthestromaofskintumours,butconfinedtothehairfollicledermalpapillainnormalpostnatalskin.CRABP2andFABP5areexpressedinthedifferentiatingcellsofsebaceousgland,interfollicularepidermisandhairfollicles,withFABP5beingaprominentmarkerofsebaceousglandsandanagenfolliclebulbs.AllthreeproteinsareupregulatedinresponsetoRAtreatmentorNotchactivationandarenegativelyregulatedbyWnt /β-cateninsignalling.Ectopicfolliclesinducedbyβ-cateninarisefromareasofthesebaceousglandthathavelostCRABP2andFABP5;相反地,inhibitionofhairfollicleformationbyN-terminallytruncatedLef1resultsinupregulationofCRABP2andFABP5.Ourfindingsdemonstratetha在不同区域软皮肤中RA信号的动态调节,为RA,β-catenin和Notch通路之间的相互作用提供了证据。

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