Faculty Profiles - TAKEICHI Takuya

Papers - TAKEICHI Takuya

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SDR9C7 catalyzes critical dehydrogenation of acylceramides for skin barrier formation Reviewed International journal

Takuya Takeichi, Tetsuya Hirabayashi, Yuki Miyasaka, Akane Kawamoto, Yusuke Okuno, Shijima Taguchi, Kana Tanahashi, Chiaki Murase, Hiroyuki Takama, Kosei Tanaka, William E. Boeglin, M. Wade Calcutt, Daisuke Watanabe, Michihiro Kono, Yoshinao Muro, Junko Ishikawa, Tamio Ohno, Alan R. Brash, Masashi Akiyama

Journal of Clinical Investigation Vol. 130 ( 2 ) page： 890 - 903 2020.2

Language：English Publishing type：Research paper (scientific journal)

© 2020, American Society for Clinical Investigation. The corneocyte lipid envelope, composed of covalently bound ceramides and fatty acids, is important to the integrity of the permeability barrier in the stratum corneum, and its absence is a prime structural defect in various skin diseases associated with defective skin barrier function. SDR9C7 encodes a short-chain dehydrogenase/reductase family 9C member 7 (SDR9C7) recently found mutated in ichthyosis. In a patient with SDR9C7 mutation and a mouse Sdr9c7-KO model, we show loss of covalent binding of epidermal ceramides to protein, a structural fault in the barrier. For reasons unresolved, protein binding requires lipoxygenase-catalyzed transformations of linoleic acid (18:2) esterified in ω-O-acylceramides. In Sdr9c7-/- epidermis, quantitative liquid chromatography-mass spectometry (LC-MS) assays revealed almost complete loss of a species of ω-Oacylceramide esterified with linoleate-9,10-trans-epoxy-11E-13-ketone; other acylceramides related to the lipoxygenase pathway were in higher abundance. Recombinant SDR9C7 catalyzed NAD+-dependent dehydrogenation of linoleate 9,10-trans-epoxy-11E-13-alcohol to the corresponding 13-ketone, while ichthyosis mutants were inactive. We propose, therefore, that the critical requirement for lipoxygenases and SDR9C7 is in producing acylceramide containing the 9,10-epoxy- 11E-13-ketone, a reactive moiety known for its nonenzymatic coupling to protein. This suggests a mechanism for coupling of ceramide to protein and provides important insights into skin barrier formation and pathogenesis.

DOI： 10.1172/JCI130675

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PubMed

A novel NCSTN missense mutation in the signal peptide domain causes hidradenitis suppurativa, which has features characteristic of an autoinflammatory keratinization disease

T. Takeichi, T. Matsumoto, T. Nomura, M. Takeda, H. Niwa, M. Kono, H. Shimizu, T. Ogi, M. Akiyama

British Journal of Dermatology Vol. 182 ( 2 ) page： 491 - 493 2020.2

Multifaceted analyses of epidermal serine protease activity in patients with atopic dermatitis Reviewed International journal

Hayato Nomura, Mutsumi Suganuma, Takuya Takeichi, Michihiro Kono, Yuki Isokane, Ko Sunagawa, Mina Kobashi, Satoru Sugihara, Ai Kajita, Tomoko Miyake, Yoji Hirai, Osamu Yamasaki, Masashi Akiyama, Shin Morizane

International Journal of Molecular Sciences Vol. 21 ( 3 ) 2020.2

Language：English Publishing type：Research paper (scientific journal)

© 2020 by the authors. Licensee MDPI, Basel, Switzerland. The serine proteases kallikrein-related peptidase (KLK) 5 and KLK7 cleave cell adhesion molecules in the epidermis. Aberrant epidermal serine protease activity is thought to play an important role in the pathogenesis of atopic dermatitis (AD). We collected the stratum corneum (SC) from healthy individuals (n = 46) and AD patients (n = 63) by tape stripping and then measuring the trypsin-and chymotrypsin-like serine protease activity. We also analyzed the p.D386N and p.E420K of SPINK5 variants and loss-of-function mutations of FLG in the AD patients. The serine protease activity in the SC was increased not only in AD lesions but also in non-lesions of AD patients. We found, generally, that there was a positive correlation between the serine protease activity in the SC and the total serum immunoglobulin E (IgE) levels, serum thymus and activation-regulated chemokine (TARC) levels, and peripheral blood eosinophil counts. Moreover, the p.D386N or p.E420K in SPINK5 and FLG mutations were not significantly associated with the SC's serine protease activity. Epidermal serine protease activity was increased even in non-lesions of AD patients. Such activity was found to correlate with a number of biomarkers of AD. Further investigations of serine proteases might provide new treatments and prophylaxis for AD.

DOI： 10.3390/ijms21030913

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PubMed

A juvenile male case of dermatofibrosarcoma protuberans on the breast

Y. Murase, T. Takeichi, T. Matsumoto, A. Sakakibara, M. Akiyama

Clinical and Experimental Dermatology Vol. 45 ( 1 ) page： 111 - 113 2020.1

Reduced stratum corneum acylceramides in autosomal recessive congenital ichthyosis with a NIPAL4 mutation Reviewed International journal

Yuya Murase, Takuya Takeichi, Akane Kawamoto, Kana Tanahashi, Yusuke Okuno, Hiroyuki Takama, Eri Shimizu, Junko Ishikawa, Tomoo Ogi, Masashi Akiyama

Journal of Dermatological Science Vol. 97 ( 1 ) page： 50 - 56 2020.1

Language：English Publishing type：Research paper (scientific journal)

© 2019 Japanese Society for Investigative Dermatology Background: NIPAL4, encoding the NIPA-like domain containing 4 protein (NIPAL4), is one of the causative genes of autosomal recessive congenital ichthyosis (ARCI). The physiological role of NIPAL4 and the pathogenetic mechanisms of ARCI caused by NIPAL4 mutations remain unclear. Objective: To clarify the changes of ceramide components in the lesional stratum corneum (SC) and the gene expression profile in the lesional skin of an ARCI patient with a novel frameshift mutation in NIPAL4. Methods: We performed ultrastructural and immunohistochemical analyses of the skin. We used RNA sequencing to determine the mRNA expression in the skin of the patient and healthy individuals. We investigated ceramide components using tape stripped SC samples from the patient. Results: mRNA expression profiling in the patient's skin showed significant upregulation of IL-17/TNFα-related genes (IL17C, IL36A, IL36G, S100A7A, S100A9) and psoriasis hallmark genes (VNN3, LCE3D, PLA2G4D), and significant downregulation of lipid-associated genes (GAL, HAO2, FABP7). Ceramide analysis in the patient's SC revealed amounts of CER[NS] with carbon chain-length (C) 32–52 were increased, while amounts of most acylceramide with C66:2 - C72:2 were reduced relatively to those in healthy individuals. After the retinoid treatment, CER[NS] with carbon chains C46–54, CER[EOH] and CER[EOP] increased. Conclusion: IL-17C and IL-36 family cytokines might be involved in the pathogenetic process of ARCI with NIPAL4 mutations. Reduced amounts of the acylceramides in the SC are associated with the skin phenotype due to NIPAL4 mutations. Efficacy of the oral retinoid treatment might be due to restored amounts of CER[EOH] and CER[EOP] in the SC.

DOI： 10.1016/j.jdermsci.2019.12.001

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PubMed

Case of erythrokeratodermia variabilis successfully treated with narrowband ultraviolet B International journal

Kayoko Okuda, Emi Nishida, Kan Tori, Akihiro Matubara, Yoko Sagawa, Takuya Takeichi, Masashi Akiyama, Akimichi Morita

Journal of Dermatology Vol. 47 ( 1 ) page： E30 - E31 2020.1

A patient with bullous pemphigoid with mucosal involvement serologically positive for anti-BP230 autoantibodies only International journal

T. Taki, T. Takeichi, M. Kono, K. Sugiura, Y. Sugimura, N. Ishii, T. Hashimoto, M. Akiyama

British Journal of Dermatology Vol. 182 ( 1 ) page： 221 - 223 2020.1

Unique reticular hyperkeratotic eruptions seen in a patient with Darier's disease and attention deficit hyperactivity disorder

T. Yoshikawa, T. Takeichi, Y. Suga, Y. Kitajima, M. Akiyama

Journal of the European Academy of Dermatology and Venereology Vol. 34 ( 1 ) page： E41 - E43 2020.1

Oculodentodigital Dysplasia Diagnosed from Severe Hypotrichosis. Reviewed International journal

Tomoki Taki, Takuya Takeichi, Kazumitsu Sugiura, Masashi Akiyama

Acta dermato-venereologica Vol. 99 ( 13 ) page： 1307 - 1308 2019.12

A case of pustular psoriasis possibly precipitated by periodic oestrogen/gestagen therapy for Turner syndrome

T. Shiratori, T. Takeichi, M. Kono, M. Nishida, A. Imanishi, N. Maekawa, N. Kawamura, K. Fukai

Clinical and Experimental Dermatology Vol. 44 ( 7 ) page： E240 - E241 2019.10

Drug-induced acute eosinophilic pneumonia due to hydroxychloroquine in a chilblain lupus patient International journal

Yuri Ishiguro, Yoshinao Muro, Chiaki Murase, Takuya Takeichi, Michihiro Kono, Runa Adachi, Kazuomi Takahashi, Masashi Akiyama

Journal of Dermatology Vol. 46 ( 10 ) page： E356 - E357 2019.10

Roles of aberrant hemichannel activities due to mutant connexin26 in the pathogenesis of KID syndrome Reviewed

Taki T., Takeichi T., Sugiura K., Akiyama M.

JOURNAL OF INVESTIGATIVE DERMATOLOGY Vol. 139 ( 9 ) page： S248 - S248 2019.9

Brooke–Spiegler syndrome with chronic obstructive pulmonary disease and chronic sinusitis International journal

Yuki Hattori, Takuya Takeichi, Masashi Akiyama, Mariko Seishima

Journal of Dermatology Vol. 46 ( 6 ) page： E200 - E202 2019.6

Unilateral case of multiple minute digitate hyperkeratosis International journal

Satoko Okochi, Michihiro Kono, Hiromichi Takama, Takuya Takeichi, Yoshinao Muro, Masashi Akiyama

Journal of Dermatology Vol. 46 ( 6 ) page： E210 - E211 2019.6

Acrodermatitis continua of Hallopeau with dense infiltration of IgG4-positive cells in the lesional dermis. Reviewed International journal

Ogawa-Momohara M, Muro Y, Nakaguro M, Takeichi T, Kono M, Akiyama M

The British journal of dermatology Vol. 180 ( 4 ) page： 941 - 942 2019.4

Aberrant CARD14 function might cause defective barrier formation International journal

Yuya Murase, Takuya Takeichi, Masashi Akiyama

Journal of Allergy and Clinical Immunology Vol. 143 ( 4 ) page： 1656 - 1657 2019.4

Familial or sporadic porokeratosis as an autoinflammatory keratinization disease International journal

Takuya Takeichi, Masashi Akiyama

Journal of Dermatology Vol. 46 ( 4 ) page： E125 - E126 2019.4

Case of adult-onset Still's disease with psoriasiform eruptions. Reviewed International journal

Yasutoshi Ito, Takuya Takeichi, Toshiko Koide, Masashi Akiyama

The Journal of dermatology Vol. 46 ( 3 ) page： E109 - E110 2019.3

Hyaline vascular-type unicentric Castleman disease presenting as a subcutaneous nodule in a child. Reviewed International journal

Takuya Hanamura, Michihiro Kono, Kenji Yokota, Takuya Takeichi, Kei Kohno, Shigeo Nakamura, Teruyuki Mitsuma, Kosei Nakajima, Yoshinao Muro, Masashi Akiyama

The Journal of dermatology Vol. 46 ( 3 ) page： E97 - E99 2019.3

The lipoxygenase-hepoxilin pathway is activated in cutaneous plaque lesions of psoriasis Reviewed

Takeichi, T; Kinoshita, F; Tanaka, H; Fujita, S; Kobayashi, Y; Nakatochi, M; Sugiura, K; Akiyama, M

JOURNAL OF CUTANEOUS IMMUNOLOGY AND ALLERGY Vol. 2 ( 1 ) page： 15 - 24 2019.2

Authorship：Lead author Language：Japanese Publisher：Journal of Cutaneous Immunology and Allergy

Psoriasis is a common skin disorder that is characterized by hyperkeratosis, epidermal hyperplasia, T-cell and neutrophil recruitment, and changes in the vascular endothelial system. The several upregulated variable lipid mediators, including the eicosanoids, in psoriatic keratinocytes were described previously, although some results were contradictory. Since hepoxilin is less stable than other eicosanoids such as hydroxyeicosatetraenoic acid (HETE), the measurement of hepoxilin is difficult. In this study, to clarify the relationship between hepoxilin/hepoxilin-related fatty acid derivatives and psoriasis vulgaris, we evaluated the amount of production of lipid mediators including hepoxilins in skin tissues of patients with psoriasis vulgaris in comparison with normal controls by high-performance liquid chromatography/mass spectrometry. Most of the hepoxilins and related lipids evaluated in this study tended to be more abundant in the lesional skin from the psoriasis patient group (PPG) than in the skin from controls. Interestingly, 12R-HETE was markedly higher in the skin samples from the PPG. In addition, the lipids produced in the lipoxygenase pathway, including hepoxilin, were elevated in the skin lesions of the PPG compared with those of normal controls, whereas the lipids produced in the cyclooxygenase pathway were decreased in the skin lesions from the PPG. Our results suggest that an imbalance between the lipoxygenase and cyclooxygenase pathways may contribute to psoriatic pathomechanisms.

DOI： 10.1002/cia2.12039

Web of Science

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Papers - TAKEICHI Takuya