Investigation of a novel lipase-like transmembrane protein for the discovery of drugs to regulate the epidermal barrier function
Project/Area Number |
15K15053
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Research Category |
Grant-in-Aid for Challenging Exploratory Research
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Allocation Type | Multi-year Fund |
Research Field |
General pharmacology
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Research Institution | Osaka University |
Principal Investigator |
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Co-Investigator(Kenkyū-buntansha) |
永森 收志 大阪大学, 医学系研究科, 准教授 (90467572)
大垣 隆一 大阪大学, 医学系研究科, 助教 (20467525)
奥田 傑 大阪大学, 医学系研究科, 助教 (50511846)
中込 咲綾 大阪大学, 微生物病研究所, 特任研究員(常勤) (60423894)
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Research Collaborator |
ISHIKAWA Junko
|
Project Period (FY) |
2015-04-01 – 2017-03-31
|
Project Status |
Completed (Fiscal Year 2016)
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Budget Amount *help |
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
|
Keywords | 表皮バリア / 角質細胞間脂質ラメラ / リパーゼ / リピドミクス |
Outline of Final Research Achievements |
The intercellular spaces in stratum corneum are filled with the lamellae of lipids, the structural entity of the epidermal barrier. We previously found that a novel lipase-like protein LIPX is essential for the epidermal barrier function. In this study, by using a LIPX gene knockout mouse strain, we investigated the mechanisms by which LIPX contributes to the formation of the lipid lamellae in the stratum corneum. We revealed that, in the absence of LIPX, the intercellular lipid lamellae formed in the stratum corneum were structurally abnormal. This defect was accompanied with a drastic decrease of ceramides that are essential for the epidermal barrier. We also demonstrated that LIPX is a transmembrane protein specifically expressed in the epidermis. The results of this study contribute to understanding the essential roles of LIPX in the epidermal barrier function and to developing novel medicines to cure the diseases with dysfunction of the epidermal barrier function.
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Report
(3 results)
Research Products
(89 results)
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[Journal Article] (18)F-FBPA as a tumor-specific probe of L-type amino acid transporter 1 (LAT1): a comparison study with (18)F-FDG and (11)C-Methionine PET.2017
Author(s)
Watabe T, Ikeda H, Nagamori S, Wiriyasermkul P, Tanaka Y, Naka S, Kanai Y, Hagiwara K, Aoki M, Shimosegawa E, Kanai Y, Hatazawa J.
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Journal Title
Eur J Nucl Med Mol Imaging.
Volume: 44
Issue: 2
Pages: 321-331
DOI
Related Report
Peer Reviewed
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[Journal Article] Increased Dynamics of Tricarboxylic Acid Cycle and Glutamate Synthesis in Obese Adipose Tissue: IN VIVO METABOLIC TURNOVER ANALYSIS.2017
Author(s)
Nagao H, Nishizawa H, Bamba T, Nakayama Y, Isozumi N, Nagamori S, Kanai Y, Tanaka Y, Kita S, Fukuda S, Funahashi T, Maeda N, Fukusaki E, Shimomura I.
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Journal Title
J Biol Chem.
Volume: 292
Issue: 11
Pages: 4469-4483
DOI
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Peer Reviewed / Open Access
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[Journal Article] Argininosuccinate Synthase 1-Deficiency Enhances the Cell Sensitivity to Arginine through Decreased DEPTOR Expression in Endometrial Cancer.2017
Author(s)
Ohshima K, Nojima S, Tahara S, Kurashige M, Hori Y, Hagiwara K, Okuzaki D, Oki S, Wada N, Ikeda JI, Kanai Y, Morii E.
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Journal Title
Sci Rep
Volume: 7
Issue: 1
Pages: 45504-45504
DOI
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Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Interaction of the Sodium/Glucose Cotransporter (SGLT) 2 inhibitor Canagliflozin with SGLT1 and SGLT2: Inhibition kinetics, sidedness of action, and transporter-associated incorporation accounting for its pharmacodynamic and pharmacokinetic features.2016
Author(s)
Ohgaki R, Wei L, Yamada K, Hara T, Kuriyama C, Okuda S, Ueta K, Shiotani M, Nagamori S, Kanai Y.
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Journal Title
J Pharmacol Exp Ther.
Volume: 358
Issue: 1
Pages: 94-102
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Core-fucosylation plays a pivotal role in hepatitis B pseudo virus infection: a possible implication for HBV glycotherapy.2016
Author(s)
Takamatsu S, Shimomura M, Kamada Y, Maeda H, Sobajima T, Hikita H, Iijima M, Okamoto Y, Misaki R, Fujiyama K, Nagamori S, Kanai Y, Takehara T, Ueda K, Kuroda S, Miyoshi E.
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Journal Title
Glycobiology.
Volume: 26
Pages: 1180-1189
DOI
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Peer Reviewed
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[Journal Article] Efficacy of system l amino acid transporter 1 inhibition as a therapeutic target in esophageal squamous cell carcinoma.2016
Author(s)
Ohshima Y, Kaira K, Yamaguchi A, Oriuchi N, Tominaga H, Nagamori S, Kanai Y, Yokobori T, Miyazaki T, Asao T, Tsushima Y, Kuwano H, Ishioka NS.
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Journal Title
Cancer Sci.
Volume: 107
Issue: 10
Pages: 1499-1505
DOI
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Peer Reviewed / Open Access
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[Journal Article] Expression of a human NPT1/SLC17A1 missense variant which increases urate export.2016
Author(s)
Sakiyama M, Matsuo H, Nagamori S, Ling W, Kawamura Y, Nakayama A, Higashino T, Chiba T, Ichida K, Kanai Y, Shinomiya N.
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Journal Title
Nucleosides Nucleotides Nucleic Acids.
Volume: 35
Pages: 536-542
Related Report
Peer Reviewed
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[Journal Article] Impaired Amino Acid Transport at the Blood Brain Barrier Is a Cause of Autism Spectrum Disorder.2016
Author(s)
Tarlungeanu DC, Deliu E, Dotter CP, Kara M, Janiesch PC, Scalise M, Galluccio M, Tesulov M, Morelli E, Sonmez FM, Bilguvar K, Ohgaki R, Kanai Y, Johansen A, Esharif S, Ben-Omran T, Topcu M, Schlessinger A, Indiveri C, Duncan KE, Caglayan AO, Gunel M, Gleeson JG, Novarino G.
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Journal Title
Cell.
Volume: 167
Issue: 6
Pages: 1481-1494
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Novel cystine transporter in renal proximal tubule identified as a missing partner of cystinuria-related plasma membrane protein rBAT/SLC3A1.2016
Author(s)
Nagamori S, Wiriyasermkul P, Guarch ME, Okuyama H, Nakagomi S, Tadagaki K, Nishinaka Y, Bodoy S, Takafuji K, Okuda S, Kurokawa J, Ohgaki R, Nunes V, Palacín M, Kanai Y.
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Journal Title
Proc Natl Acad Sci U S A.
Volume: 113
Issue: 3
Pages: 775-780
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] Transport of 3-fluoro-l-α-methyl-tyrosine (FAMT) by organic ion transporters explains renal background in [(18)F]FAMT positron emission tomography.2016
Author(s)
Wei L, Tominaga H, Ohgaki R, Wiriyasermkul P, Hagiwara K, Okuda S, Kaira K, Kato Y, Oriuchi N, Nagamori S, Kanai Y.
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Journal Title
J Pharmacol Sci.
Volume: 130
Issue: 2
Pages: 101-109
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] Development of a Widely Usable Amino Acid Tracer: 76Br-α-Methyl-Phenylalanine for Tumor PET Imaging.2015
Author(s)
Hanaoka H, Ohshima Y, Suzuki Y, Yamaguchi A, Watanabe S, Uehara T, Nagamori S, Kanai Y, Ishioka NS, Tsushima Y, Endo K, Arano Y
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Journal Title
J Nucl Med.
Volume: 56
Issue: 5
Pages: 791-797
DOI
Related Report
Peer Reviewed
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[Journal Article] Expression of Amino Acid Transporters (LAT1 and ASCT2) in Patients with Stage III/IV Laryngeal Squamous Cell Carcinoma.2015
Author(s)
Nikkuni O, Kaira K, Toyoda M, Shino M, Sakakura K, Takahashi K, Tominaga H, Oriuchi N, Suzuki M, Iijima M, Asao T, Nishiyama M, Nagamori S, Kanai Y, Oyama T, Chikamatsu K.
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Journal Title
Pathol Oncol Res
Volume: 21
Issue: 4
Pages: 1175-1181
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Molecular architecture of the stria vascularis membrane transport system, which is essential for physiological functions of the mammalian cochlea.2015
Author(s)
Uetsuka S, Ogata G, Nagamori S, Isozumi N, Nin F, Yoshida T, Komune S, Kitahara T, Kikkawa Y, Inohara H, Kanai Y, Hibino H.
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Journal Title
Eur J Neurosci.
Volume: 42
Issue: 3
Pages: 1984-2002
DOI
Related Report
Peer Reviewed
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[Journal Article] Prognostic significance of L-type amino acid transporter 1 (LAT1) expression in cutaneous melanoma.2015
Author(s)
Shimizu A, Kaira K, Kato M, Yasuda M, Takahashi A, Tominaga H, Oriuchi N, Nagamori S, Kanai Y, Oyama T, Asao T, Ishikawa O.
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Journal Title
Melanoma Res.
Volume: 25
Issue: 5
Pages: 399-405
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] CD98 as a novel prognostic indicator for patients with stage III/IV hypopharyngeal squamous cell carcinoma.2014
Author(s)
Toyoda M, Kaira K, Shino M, Sakakura K, Takahashi K, Takayasu Y, Tominaga H, Oriuchi N, Nikkuni O, Suzuki M, Iijima M, Tsukamoto N, Nagamori S, Kanai Y, Oyama T, Chikamatsu K.
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Journal Title
Head Neck.
Volume: in press
Issue: 11
Pages: 1-6
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Presentation] Inhibition kinetics, sidedness of action, and transporter-mediated uptake of the sodium/glucose cotransporter (SGLT) 2 inhibitor canagliflozin: implications for its pharmacodynamic and pharmacokinetic features2016
Author(s)
Ling Wei, Ryuichi Ohgaki, Kazunori Yamada, Taiki Hara, Chiaki Kuriyama, Suguru Okuda, Kiichiro Ueta, Masaharu shiotani, Shushi Nagamori and Yoshikatsu Kanai
Organizer
International and Interdisciplinary Symposium 2016 “Towards a New Era of Cardiovascular Research”
Place of Presentation
東京
Year and Date
2016-07-12
Related Report
Int'l Joint Research
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[Presentation] Inhibition kinetics, sidedness of action, and transporter-mediated uptake of the sodium/glucose cotransporter (SGLT) 2 inhibitor canagliflozin: implications for its pharmacodynamic and pharmacokinetic features2016
Author(s)
Ohgaki R, Wei L, Yamada K, Hara T, Kuriyama C, Okuda S, Ueta K, Leclercq L, Mamidi RN, Shiotani M, Nagamori S, Kanai Y
Organizer
76th American Diabetes Association Scientific Sessions
Place of Presentation
New Orleans, Louisiana, US
Year and Date
2016-06-10
Related Report
Int'l Joint Research
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