Disruption of the Sjögren-Larsson syndrome gene Aldh3a2 in mice increases keratinocyte growth and retards skin barrier recovery

Tatsuro Naganuma, Shuyu Takagi, Tsukasa Kanetake, Takuya Kitamura, Satoko Takai, Tsuyoshi Miyakawa, Takayuki Sassa, Akio Kihara

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

The fatty aldehyde dehydrogenase (FALDH) ALDH3A2 is the causative gene of Sjögren Larsson syndrome (SLS). To date, the molecular mechanism underlying the symptoms characterizing SLS has been poorly understood. Using Aldh3a2-/- mice, we found here that Aldh3a2 was the major FALDH active in undifferentiated keratinocytes. Long-chain base metabolism was greatly impaired in Aldh3a2-/- keratinocytes. Phenotypically, the intercellular spaces were widened in the basal layer of the Aldh3a2-/- epidermis due to hyperproliferation of keratinocytes. Furthermore, oxidative stress-induced genes were upregulated in Aldh3a2-/- keratinocytes. Upon keratinocyte differentiation, the activity of another FALDH, Aldh3b2, surpassed that of Aldh3a2. As a result, Aldh3a2-/- mice were indistinguishable from wild-type mice in terms of their whole epidermis FALDH activity, and their skin barrier function was uncompromised under normal conditions. However, perturbation of the stratum corneum caused increased transepidermal water loss and delayed barrier recovery in Aldh3a2-/- mice. In conclusion, Aldh3a2-/- mice replicated some aspects of SLS symptoms, especially at the basal layer of the epidermis. Our results suggest that hyperproliferation of keratinocytes via oxidative stress responses may partly contribute to the ichthyosis symptoms of SLS.

Original languageEnglish
Pages (from-to)11676-11688
Number of pages13
JournalJournal of Biological Chemistry
Volume291
Issue number22
DOIs
Publication statusPublished - 27-05-2016

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long-chain-aldehyde dehydrogenase
Keratinocytes
Skin
Genes
Recovery
Growth
Epidermis
Oxidative stress
Oxidative Stress
Ichthyosis
Extracellular Space
Metabolism
Cornea
Water

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Naganuma, Tatsuro ; Takagi, Shuyu ; Kanetake, Tsukasa ; Kitamura, Takuya ; Takai, Satoko ; Miyakawa, Tsuyoshi ; Sassa, Takayuki ; Kihara, Akio. / Disruption of the Sjögren-Larsson syndrome gene Aldh3a2 in mice increases keratinocyte growth and retards skin barrier recovery. In: Journal of Biological Chemistry. 2016 ; Vol. 291, No. 22. pp. 11676-11688.
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abstract = "The fatty aldehyde dehydrogenase (FALDH) ALDH3A2 is the causative gene of Sj{\"o}gren Larsson syndrome (SLS). To date, the molecular mechanism underlying the symptoms characterizing SLS has been poorly understood. Using Aldh3a2-/- mice, we found here that Aldh3a2 was the major FALDH active in undifferentiated keratinocytes. Long-chain base metabolism was greatly impaired in Aldh3a2-/- keratinocytes. Phenotypically, the intercellular spaces were widened in the basal layer of the Aldh3a2-/- epidermis due to hyperproliferation of keratinocytes. Furthermore, oxidative stress-induced genes were upregulated in Aldh3a2-/- keratinocytes. Upon keratinocyte differentiation, the activity of another FALDH, Aldh3b2, surpassed that of Aldh3a2. As a result, Aldh3a2-/- mice were indistinguishable from wild-type mice in terms of their whole epidermis FALDH activity, and their skin barrier function was uncompromised under normal conditions. However, perturbation of the stratum corneum caused increased transepidermal water loss and delayed barrier recovery in Aldh3a2-/- mice. In conclusion, Aldh3a2-/- mice replicated some aspects of SLS symptoms, especially at the basal layer of the epidermis. Our results suggest that hyperproliferation of keratinocytes via oxidative stress responses may partly contribute to the ichthyosis symptoms of SLS.",
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Disruption of the Sjögren-Larsson syndrome gene Aldh3a2 in mice increases keratinocyte growth and retards skin barrier recovery. / Naganuma, Tatsuro; Takagi, Shuyu; Kanetake, Tsukasa; Kitamura, Takuya; Takai, Satoko; Miyakawa, Tsuyoshi; Sassa, Takayuki; Kihara, Akio.

In: Journal of Biological Chemistry, Vol. 291, No. 22, 27.05.2016, p. 11676-11688.

Research output: Contribution to journalArticle

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T1 - Disruption of the Sjögren-Larsson syndrome gene Aldh3a2 in mice increases keratinocyte growth and retards skin barrier recovery

AU - Naganuma, Tatsuro

AU - Takagi, Shuyu

AU - Kanetake, Tsukasa

AU - Kitamura, Takuya

AU - Takai, Satoko

AU - Miyakawa, Tsuyoshi

AU - Sassa, Takayuki

AU - Kihara, Akio

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N2 - The fatty aldehyde dehydrogenase (FALDH) ALDH3A2 is the causative gene of Sjögren Larsson syndrome (SLS). To date, the molecular mechanism underlying the symptoms characterizing SLS has been poorly understood. Using Aldh3a2-/- mice, we found here that Aldh3a2 was the major FALDH active in undifferentiated keratinocytes. Long-chain base metabolism was greatly impaired in Aldh3a2-/- keratinocytes. Phenotypically, the intercellular spaces were widened in the basal layer of the Aldh3a2-/- epidermis due to hyperproliferation of keratinocytes. Furthermore, oxidative stress-induced genes were upregulated in Aldh3a2-/- keratinocytes. Upon keratinocyte differentiation, the activity of another FALDH, Aldh3b2, surpassed that of Aldh3a2. As a result, Aldh3a2-/- mice were indistinguishable from wild-type mice in terms of their whole epidermis FALDH activity, and their skin barrier function was uncompromised under normal conditions. However, perturbation of the stratum corneum caused increased transepidermal water loss and delayed barrier recovery in Aldh3a2-/- mice. In conclusion, Aldh3a2-/- mice replicated some aspects of SLS symptoms, especially at the basal layer of the epidermis. Our results suggest that hyperproliferation of keratinocytes via oxidative stress responses may partly contribute to the ichthyosis symptoms of SLS.

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