Loricrin and NRF2 Coordinate Cornification

Cornification involves cytoskeletal cross-linkages in corneocytes (the brick) and the secretion of lipids/adhesion structures to the interstitial space (the mortar). Because the assembly of lipid envelopes precedes corneocyte maturation, loricrin is supposed to be dispensable for the protection agai...

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Autores principales:	Yosuke Ishitsuka, Tatsuya Ogawa, Yoshiyuki Nakamura, Noriko Kubota, Yasuhiro Fujisawa, Rei Watanabe, Naoko Okiyama, Manabu Fujimoto, Dennis R. Roop, Akemi Ishida-Yamamoto
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2022
Materias:	Dermatology RL1-803
Acceso en línea:	https://doaj.org/article/3f586b8bb46046aeb57214cd1957d59e
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spelling	oai:doaj.org-article:3f586b8bb46046aeb57214cd1957d59e2021-11-12T04:49:42ZLoricrin and NRF2 Coordinate Cornification2667-026710.1016/j.xjidi.2021.100065https://doaj.org/article/3f586b8bb46046aeb57214cd1957d59e2022-01-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2667026721000667https://doaj.org/toc/2667-0267Cornification involves cytoskeletal cross-linkages in corneocytes (the brick) and the secretion of lipids/adhesion structures to the interstitial space (the mortar). Because the assembly of lipid envelopes precedes corneocyte maturation, loricrin is supposed to be dispensable for the protection against desiccation. Although the phenotypes of Lor knockout (LKO) mice are obscure, the antioxidative response on the KEAP1/NRF2 signaling pathway compensates for the structural defect in utero. In this study, we asked how the compensatory response is evoked after the defects are repaired. To this end, the postnatal phenotypes of LKO mice were analyzed with particular attention to the permeability barrier function primarily maintained by the mortar. Ultrastructural analysis revealed substantially thinner cornified cell envelopes and increased numbers of lamellar granules in LKO mice. Superficial epidermal damages triggered the adaptive repairing responses that evoke the NRF2-dependent upregulation of genes associated with lamellar granule secretion in LKO mice. We also found that corneodesmosomes are less degraded in LKO mice. The observation suggests that loricrin and NRF2 are important effectors of cornification, in which proteins need to be secreted, cross-linked, and degraded in a coordinated manner.Yosuke IshitsukaTatsuya OgawaYoshiyuki NakamuraNoriko KubotaYasuhiro FujisawaRei WatanabeNaoko OkiyamaManabu FujimotoDennis R. RoopAkemi Ishida-YamamotoElsevierarticleDermatologyRL1-803ENJID Innovations, Vol 2, Iss 1, Pp 100065- (2022)
institution	DOAJ
collection	DOAJ
language	EN
topic	Dermatology RL1-803
spellingShingle	Dermatology RL1-803 Yosuke Ishitsuka Tatsuya Ogawa Yoshiyuki Nakamura Noriko Kubota Yasuhiro Fujisawa Rei Watanabe Naoko Okiyama Manabu Fujimoto Dennis R. Roop Akemi Ishida-Yamamoto Loricrin and NRF2 Coordinate Cornification
description	Cornification involves cytoskeletal cross-linkages in corneocytes (the brick) and the secretion of lipids/adhesion structures to the interstitial space (the mortar). Because the assembly of lipid envelopes precedes corneocyte maturation, loricrin is supposed to be dispensable for the protection against desiccation. Although the phenotypes of Lor knockout (LKO) mice are obscure, the antioxidative response on the KEAP1/NRF2 signaling pathway compensates for the structural defect in utero. In this study, we asked how the compensatory response is evoked after the defects are repaired. To this end, the postnatal phenotypes of LKO mice were analyzed with particular attention to the permeability barrier function primarily maintained by the mortar. Ultrastructural analysis revealed substantially thinner cornified cell envelopes and increased numbers of lamellar granules in LKO mice. Superficial epidermal damages triggered the adaptive repairing responses that evoke the NRF2-dependent upregulation of genes associated with lamellar granule secretion in LKO mice. We also found that corneodesmosomes are less degraded in LKO mice. The observation suggests that loricrin and NRF2 are important effectors of cornification, in which proteins need to be secreted, cross-linked, and degraded in a coordinated manner.
format	article
author	Yosuke Ishitsuka Tatsuya Ogawa Yoshiyuki Nakamura Noriko Kubota Yasuhiro Fujisawa Rei Watanabe Naoko Okiyama Manabu Fujimoto Dennis R. Roop Akemi Ishida-Yamamoto
author_facet	Yosuke Ishitsuka Tatsuya Ogawa Yoshiyuki Nakamura Noriko Kubota Yasuhiro Fujisawa Rei Watanabe Naoko Okiyama Manabu Fujimoto Dennis R. Roop Akemi Ishida-Yamamoto
author_sort	Yosuke Ishitsuka
title	Loricrin and NRF2 Coordinate Cornification
title_short	Loricrin and NRF2 Coordinate Cornification
title_full	Loricrin and NRF2 Coordinate Cornification
title_fullStr	Loricrin and NRF2 Coordinate Cornification
title_full_unstemmed	Loricrin and NRF2 Coordinate Cornification
title_sort	loricrin and nrf2 coordinate cornification
publisher	Elsevier
publishDate	2022
url	https://doaj.org/article/3f586b8bb46046aeb57214cd1957d59e
work_keys_str_mv	AT yosukeishitsuka loricrinandnrf2coordinatecornification AT tatsuyaogawa loricrinandnrf2coordinatecornification AT yoshiyukinakamura loricrinandnrf2coordinatecornification AT norikokubota loricrinandnrf2coordinatecornification AT yasuhirofujisawa loricrinandnrf2coordinatecornification AT reiwatanabe loricrinandnrf2coordinatecornification AT naokookiyama loricrinandnrf2coordinatecornification AT manabufujimoto loricrinandnrf2coordinatecornification AT dennisrroop loricrinandnrf2coordinatecornification AT akemiishidayamamoto loricrinandnrf2coordinatecornification
_version_	1718431163449606144

Loricrin and NRF2 Coordinate Cornification

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