Lce1 Family Members Are Nrf2-Target Genes that Are Induced to Compensate for the Loss of Loricrin

Yosuke Ishitsuka, Aaron J. Huebner, Robert H. Rice, Peter J. Koch, Vladislav V. Speransky, Alasdair C. Steven, Dennis R. Roop

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Loricrin is a major component of the cornified cell envelope, a highly insoluble structure composed of covalently cross-linked proteins. Although loricrin knockout mice only exhibit a mild transient phenotype at birth, they show a marked delay in the formation of an epidermal barrier in utero. We recently discovered that induction of a compensatory response to repair the defective barrier is initiated by amniotic fluid via activation of NF-E2-related factor 2 and identified Sprr2d and Sprr2h as direct transcriptional targets. Proteomic analysis suggested that other proteins were also incorporated into the loricrin knockout cell envelope, in addition to the small proline rich proteins. Here we present evidence suggesting that the late cornified envelope 1 proteins are also compensatory components as determined by their localization within the loricrin knockout cell envelope via immunoelectron microscopy. We also demonstrate that late cornified envelope 1 genes are upregulated at the transcriptional level in loricrin knockout mouse skin and confirm that late cornified envelope 1 genes are transcriptional targets of NRF2. Our present study further highlights the complexity and importance of a compensatory mechanism that evolved in terrestrial animals to ensure the formation of a functional epidermal barrier.

Original languageEnglish (US)
Pages (from-to)1656-1663
Number of pages8
JournalJournal of Investigative Dermatology
Volume136
Issue number8
DOIs
StatePublished - Aug 1 2016

Fingerprint

Genes
Knockout Mice
Proteins
NF-E2-Related Factor 2
Immunoelectron Microscopy
Cellular Structures
Amniotic Fluid
Proline
Proteomics
Skin
Microscopic examination
Animals
Repair
Chemical activation
loricrin
Parturition
Phenotype
Fluids

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

Cite this

Ishitsuka, Y., Huebner, A. J., Rice, R. H., Koch, P. J., Speransky, V. V., Steven, A. C., & Roop, D. R. (2016). Lce1 Family Members Are Nrf2-Target Genes that Are Induced to Compensate for the Loss of Loricrin. Journal of Investigative Dermatology, 136(8), 1656-1663. https://doi.org/10.1016/j.jid.2016.04.022

Lce1 Family Members Are Nrf2-Target Genes that Are Induced to Compensate for the Loss of Loricrin. / Ishitsuka, Yosuke; Huebner, Aaron J.; Rice, Robert H.; Koch, Peter J.; Speransky, Vladislav V.; Steven, Alasdair C.; Roop, Dennis R.

In: Journal of Investigative Dermatology, Vol. 136, No. 8, 01.08.2016, p. 1656-1663.

Research output: Contribution to journalArticle

Ishitsuka, Y, Huebner, AJ, Rice, RH, Koch, PJ, Speransky, VV, Steven, AC & Roop, DR 2016, 'Lce1 Family Members Are Nrf2-Target Genes that Are Induced to Compensate for the Loss of Loricrin', Journal of Investigative Dermatology, vol. 136, no. 8, pp. 1656-1663. https://doi.org/10.1016/j.jid.2016.04.022
Ishitsuka, Yosuke ; Huebner, Aaron J. ; Rice, Robert H. ; Koch, Peter J. ; Speransky, Vladislav V. ; Steven, Alasdair C. ; Roop, Dennis R. / Lce1 Family Members Are Nrf2-Target Genes that Are Induced to Compensate for the Loss of Loricrin. In: Journal of Investigative Dermatology. 2016 ; Vol. 136, No. 8. pp. 1656-1663.
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