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Disruption of the Sjogren-Larsson Syndrome Gene Aldh3a2 in Mice Increases Keratinocyte Growth and Retards Skin Barrier Recovery
| Title: | Disruption of the Sjogren-Larsson Syndrome Gene Aldh3a2 in Mice Increases Keratinocyte Growth and Retards Skin Barrier Recovery |
| Authors: | Naganuma, Tatsuro Browse this author | | Takagi, Shuyu Browse this author | | Kanetake, Tsukasa Browse this author | | Kitamura, Takuya Browse this author | | Hattori, Satoko Browse this author →KAKEN DB | | Miyakawa, Tsuyoshi Browse this author →KAKEN DB | | Sassa, Takayuki Browse this author →KAKEN DB | | Kihara, Akio Browse this author →KAKEN DB |
| Issue Date: | 27-May-2016 |
| Publisher: | American Society for Biochemistry and Molecular Biology (ASBMB) |
| Journal Title: | Journal of Biological Chemistry (JBC) |
| Volume: | 291 |
| Issue: | 22 |
| Start Page: | 11676 |
| End Page: | 11688 |
| Publisher DOI: | 10.1074/jbc.M116.714030 |
| Abstract: | The fatty aldehyde dehydrogenase (FALDH) ALDH3A2 is the causative gene of Sjogren 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. |
| Rights: | This research was originally published in Journal of Biological Chemistry. Tatsuro Naganuma, Shuyu Takagi, Tsukasa Kanetake, Takuya Kitamura, Satoko Hattori, Tsuyoshi Miyakawa, Takayuki Sassa and Akio Kihara. Disruption of the Sjogren-Larsson Syndrome Gene Aldh3a2 in Mice Increases Keratinocyte Growth and Retards Skin Barrier Recovery. Journal of Biological Chemistry. 2016; Vol.291:11676-11688. ©the American Society for Biochemistry and Molecular Biology. |
| Type: | article |
| URI: | http://hdl.handle.net/2115/65670 |
| Appears in Collections: | 薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 木原 章雄
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