In epidermis, the last steps of keratinocyte differentiation are characterized by the covalent cross-linking of cornified envelope precursors such as
involucrin and
loricrin, a hydrophobic
protein recently described in mouse and human epidermis. In situ hybridization of normal human skin sections with a human
loricrin cRNA probe and immunolabeling with an antiserum directed against a synthetic
peptide corresponding to the carboxyterminus of human
loricrin revealed the presence of
loricrin transcripts and
protein in the granular layers of epidermis. In human epidermis reconstructed in vitro by growing keratinocytes on dermal equivalents,
loricrin and
loricrin mRNAs were also restricted to granular cells, but their amounts seemed higher than in epidermis from skin biopsies. The reactivities for both
loricrin and
loricrin mRNAs were abolished by a treatment of the cultures with a
retinoic acid concentration (10(-6) M) provoking a complete inhibition of terminal epidermal differentiation (
parakeratosis). Thus, the regulation of
loricrin synthesis is different from that of another envelope precursor,
involucrin, which does not seem to be significantly modulated by
retinoic acid. Together with the well-documented inhibition of epidermal
transglutaminase by
retinoic acid, our results provide a molecular basis for the inhibition of cornified envelope formation by
retinoic acid.