RRC ID 36839
著者 Naganuma T, Takagi S, Kanetake T, Kitamura T, Hattori S, Miyakawa T, Sassa T, Kihara A.
タイトル Disruption of the Sjögren-Larsson Syndrome Gene Aldh3a2 in Mice Increases Keratinocyte Growth and Retards Skin Barrier Recovery.
ジャーナル J Biol Chem
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 up-regulated 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.
巻・号 291(22)
ページ 11676-88
公開日 2016-5-27
DOI 10.1074/jbc.M116.714030
PII S0021-9258(20)43198-9
PMID 27053112
PMC PMC4882436
MeSH Aldehyde Oxidoreductases / genetics Aldehyde Oxidoreductases / metabolism* Aldehyde Oxidoreductases / physiology* Animals Apoptosis Blotting, Western Cell Membrane Permeability* Cell Proliferation Cells, Cultured Female Keratinocytes / cytology* Keratinocytes / metabolism Male Mice Mice, Inbred C57BL Mice, Knockout RNA, Messenger / genetics Real-Time Polymerase Chain Reaction Reverse Transcriptase Polymerase Chain Reaction Sjogren-Larsson Syndrome / etiology Sjogren-Larsson Syndrome / pathology* Skin / metabolism Skin / pathology*
IF 4.238
引用数 12
WOS 分野 BIOCHEMISTRY & MOLECULAR BIOLOGY
リソース情報
実験動物マウス RBRC01828