(a) Immunohistochemistry was performed on formalin-fixed paraffin-embedded sections from back skin. Nuclear accumulation of NRF2 was seen in LKO epidermis. Scale bars = 20 μm. (b) Nuclear protein fractions were extracted from back skin and subjected to immunoblotting. LKO nuclear extracts showed a higher level of NRF2 protein. (c) Analysis of mRNA extracted from back skin by qRT-PCR. There was a statistically significant upregulation of Nqo1, Sprr2d, and Sprr2h genes, validated NRF2 downstream targets, in addition to the Nrf2 gene itself, in LKO skin. The transcripts of Lce1b, c, e, g, h, and m were significantly increased in LKO versus WT skin (WT n = 8, LKO n = 8, *P < 0.05, **P < 0.01, ***P < 0.005, ****P < 0.001). LCE, late cornified envelope; LKO, loricrin knockout; NRF2, NF-E2-related factor 2; qRT-PCR, quantitative real-time PCR; WT, wild type.