Figure 3.

Downregulation of cornified envelope components in skin diseases and experimental conditions related to epidermal barrier dysfunction. Cornified envelopes are composed of various molecules, such as involucrin, loricrin, small proline-rich proteins (SPRRs), envoplakin, periplakin, and cysteine protease inhibitor A (cystatin A), crossed-linked by transglutaminases (TGases). Loss-of-function mutations in SPRR/SPRR3, LOR (encoding loricrin), TGM1/TGM5 (encoding transglutaminase1/5), and CSTA (encoding cystatin A) have been associated with atopic dermatitis (AD) or ichthyoses. Expression levels of loricrin and SPRRs have been reduced in experimental conditions of the disrupted epidermal barrier by retinoic acid (RA) application. Although triple knocking-out of envoplakin, periplakin, and involucrin induces abnormal cornified envelopes, mutations or deficiencies of involucrin alone do not cause atopic dermatitis.