The loss of desmosomes after retinoic acid treatment results in an apparent inhibition of HaCaT keratinocyte differentiation

Epithelial tissue cohesion is based on various types of intercellular adher ing junctions of which the desmosomes are particularly abundant in stratifi ed epithelia, The desmogleins (dsg) and desmocollins are their transmembran e components. One or more of the three isoforms of these desmosomal cadheri ns are coexpressed and specific subtypes prevail at different stages of epi dermal differentiation. In HaCaT keratinocytes, desmosomal cadherin express ion increased with ongoing differentiation, apart from dsg2, Continuous tre atment with retinoic acid(RA) inhibits the differentiation of HaCaT keratin ocyte cultures, RA strongly increased the shedding of cells into the cultur e. medium where they quickly underwent cellular death. Electron microscopy showed a marked reduction of desmosomes with nearly complete absence of the ir structural components, suggesting that RA inhibits their synthesis. RA i ndeed downregulated the transcript levels of all HaCaT desmosomal cadherins , except dsg2, Immunostaining revealed that desmosomal protein contents cor responded to alterations in transcription rates. Our findings indicate that the RA-induced inhibition of differentiation of keratinocyte cultures resu lts from removal of cells committed to differentiation. In vivo, less adher ing but still differentiating cells cannot be removed as easily as they can be in a culture system, The consequence is a sticky and fragile skin.