Details of a Researcher - Chikuma, Mariko

Papers - Chikuma, Mariko

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Glycerol enhances mitochondrial metabolism and inflammatory response in pro-inflammatory macrophages.

Manami Tanaka, Takako Hishiki, Tomomi Matsuura, Masato Yasui, Shunsuke Chikuma, Mariko Hara-Chikuma

EMBO reports 2026.04

Last author, Corresponding author, ISSN 1469-221X

Although glycerol is a ubiquitous metabolite in mammalian systems, its cellular metabolic pathways and functions have not been fully elucidated. Here, we find that elevated extracellular glycerol modulates intracellular metabolism and pro-inflammatory responses of macrophages. In pro-inflammatory macrophages stimulated with lipopolysaccharide, glycerol is taken up through glycerol channels including Aquaporin 3 (AQP3) and metabolized to glycerol-3-phosphate (G3P), which is then converted to dihydroxyacetone phosphate by glycerol-3-phosphate dehydrogenase 2 (GPD2). This glycerol-driven pathway enhances mitochondrial ATP production, potentially by supplying electrons to the electron transport chain (ETC) via GPD2, and by upregulating the transcription of genes encoding ETC complexes. In addition, glycerol supplementation elevates intracellular acetyl-CoA levels, promotes histone acetylation at the promoters of pro-inflammatory cytokine genes, and consequently increases cytokine gene expression, suggesting enhanced pro-inflammatory response. In vivo experiments, macrophage-specific AQP3 conditional knockout mice exhibit reduced weight gain and adipose tissue inflammation in a high-fat diet-induced obesity model. Our findings provide novel insights into the metabolic regulation and macrophage inflammation by extracellular glycerol.

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Aquaporin 3 inhibition attenuates imiquimod-induced psoriatic symptoms in a murine model.

Ryosuke Okubo, Manami Tanaka, Akiharu Kubo, Masato Yasui, Mariko Hara-Chikuma

Molecular biology reports 52 ( 1 ) 354 - 354 2025.04

Last author, Corresponding author, ISSN 0301-4851

BACKGROUND: Aquaporin 3 (AQP3) is highly expressed in both keratinocytes and T cells within psoriatic skin. Previous studies have demonstrated that AQP3 knockout mice show reduced development of psoriatic symptoms in murine models. This study aims to evaluate the effect of AQP3 inhibition on psoriasis progression. METHODS AND RESULTS: AQP3 conditional knockout mice were generated to assess the role of AQP3 expression in keratinocytes and T cells in psoriasis pathogenesis. In an imiquimod (IMQ)-induced psoriasis model, psoriatic symptoms were significantly reduced in mice with keratinocyte-specific AQP3 deletion. Additionally, AQP3 inhibition by administration of anti-AQP3 monoclonal antibody (mAb) effectively alleviated IMQ-induced psoriasis symptoms in wild-type mice. CONCLUSIONS: AQP3 inhibition presents a promising approach for the treatment of psoriasis.

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HSP90 promotes tumor associated macrophage differentiation during triple-negative breast cancer progression.

Lingjia Hong, Manami Tanaka, Masato Yasui, Mariko Hara-Chikuma

Scientific reports 14 ( 1 ) 22541 - 22541 2024.09

Last author, Corresponding author

Tumor-associated macrophages (TAMs) originating from monocytes are crucial for cancer progression; however, the mechanism of TAM differentiation is unclear. We investigated factors involved in the differentiation of monocytes into TAMs within the tumor microenvironment of triple-negative breast cancer (TNBC). We screened 172 compounds and found that a heat shock protein 90 (HSP90) inhibitor blocked TNBC-induced monocyte-to-TAM differentiation in human monocytes THP-1. TNBC-derived conditional medium (CM) activated cell signaling pathways, including MAP kinase, AKT and STAT3, and increased the expression of TAM-related genes and proteins. These inductions were suppressed by HSP90 inhibition or by knockdown of HSP90 in TNBC. Additionally, we confirmed that TNBC secreted HSP90 extracellularly and that HSP90 itself promoted TAM differentiation. In a mouse tumor model, treatment with an HSP90 inhibitor suppressed tumor growth and reduced TAMs in the tumor microenvironment. Our findings demonstrate the role of HSP90 in TAM differentiation, suggesting HSP90 as a potential target for TNBC immunotherapy due to its regulatory role in monocyte-to-TAM differentiation.

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Sufficient water intake maintains the gut microbiota and immune homeostasis and promotes pathogen elimination.

Kensuke Sato, Mariko Hara-Chikuma, Masato Yasui, Joe Inoue, Yun-Gi Kim

iScience 27 ( 6 ) 109903 - 109903 2024.06

Accepted

Water is the most abundant substance in the human body and plays a pivotal role in various bodily functions. While underhydration is associated with the incidence of certain diseases, the specific role of water in gut function remains largely unexplored. Here, we show that water restriction disrupts gut homeostasis, which is accompanied by a bloom of gut microbes and decreased numbers of immune cells, especially Th17 cells, within the colon. These microbial and immunological changes in the gut are associated with an impaired ability to eliminate the enteric pathogen Citrobacter rodentium. Moreover, aquaporin 3, a water channel protein, is required for the maintenance of Th17 cell function and differentiation. Taken together, adequate water intake is critical for maintaining bacterial and immunological homeostasis in the gut, thereby enhancing host defenses against enteric pathogens.

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Targeting abatacept-resistant T-helper-17 cells by aldehyde dehydrogenase inhibition.

By Yukiko Tokifuji, Hodaka Hayabuchi, Takashi Sasaki, Mariko Hara-Chikuma, Keiji Hirota, Hayato Takahashi, Masayuki Amagai, Akihiko Yoshimura, Shunsuke Chikuma

iScience 27 ( 1 ) 108646 - 108646 2024.01

Accepted

IL-17-producing helper T (Th17) cells are long-lived and serve as central effector cells in chronic autoimmune diseases. The underlying mechanisms of Th17 persistence remain unclear. We demonstrated that abatacept, a CD28 antagonist, effectively prevented the development of skin disease in a Th17-dependent experimental autoimmune dermatitis model. Abatacept selectively inhibited the emergence of IL-7R-negative effector-phenotype T cells while allowing the survival and proliferation of IL-7R+ memory-phenotype cells. The surviving IL-7R+ Th17 cells expressed genes associated with alcohol/aldehyde detoxification and showed potential to transdifferentiate into IL-7R-negative effector cells. Inhibiting aldehyde dehydrogenase reduced IL-7R+ Th17 cells in vivo, independently of CD28, and exhibited additive effects when combined with abatacept. Our findings suggest that CD28 blockade prevents inflammation without eliminating persistent memory cells. These remaining memory cells can be targeted by other drugs, such as aldehyde dehydrogenase inhibitors, to limit their survival, thereby facilitating the treatment of chronic autoimmune diseases.

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Aquaporin 3 inhibition suppresses the mitochondrial respiration rate and viability of multiple myeloma cells.

Manami Tanaka, Masato Yasui, Mariko Hara-Chikuma

Biochemical and biophysical research communications 676 158 - 164 2023.07

Last author, Corresponding author, Accepted, ISSN 0006-291X

Aquaporin 3 (AQP3) is a member of the aquaporin water channel family expressed by numerous cell types, including some cancer cells. Accumulating evidence suggests that AQP3 inhibition may impede cancer progression, but drugs targeting AQP3 are still in the early pre-clinical stage of development. Here, we examined the effect of AQP3 inhibition on multiple myeloma (MM), an incurable plasma cell malignancy. Four MM cell lines were cultured in the presence of an anti-AQP3 monoclonal antibody (mAb), the AQP3 inhibitor DFP00173, or corresponding controls, and the effects on cell viability, proliferation, apoptosis, and mitochondrial respiration capacity were compared. Both anti-AQP3 mAb and DFP00173 reduced cell growth, mitochondrial respiration rate, and electron transport chain complex I activity. Both agents also potentiated the antiproliferative efficacy of the anticancer drug venetoclax. Administration of the anti-AQP3 mAb to immunodeficient mice inoculated with RPMI8226 or KMS-11 MM cells significantly suppressed tumor growth. These data provide evidence that AQP3 blockade can suppress MM cell growth in vitro and tumor growth in mice. Thus, AQP3 inhibition may be an effective therapeutic strategy for MM.

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Anti-tumor effect of aquaporin 3 monoclonal antibody on syngeneic mouse tumor model

Manami Tanaka, Anmi Ito, Seiji Shiozawa, Mariko Hara-Chikuma

Translational Oncology (Elsevier BV) 24 101498 - 101498 2022.10

Last author, Corresponding author, Accepted, ISSN 1936-5233

Aquaporin-3 (AQP3), a water channel protein, has been found to be involved in cancer progression via water and small molecule transport function. However, drug development targeting AQP3 has not yet begun. Here, we showed that a recently established anti-AQP3 monoclonal antibody (mAb) suppresses tumor growth in allograft mouse colorectal tumor models produced using CT26 or MC38 cancer cells. Administration of the anti-AQP3 mAb to BALB/c mice with transplanted CT26 cells increased the M1/M2 ratio of tumor-associated macrophages (TAM) and improved the mitochondrial function of T cells in the tumor microenvironment (TME). Administration of anti-AQP3 mAb also restored the TAM-induced decrease in T cell proliferation. Macrophage depletion in wild-type mice counteracted the antitumor effect of anti-AQP3 mAb in the mouse tumor model, suggesting that one of the primary targets of anti-AQP3 mAb is macrophages. In in vitro studies using mice bone marrow monocytes and human monocyte THP-1 cells, anti-AQP3 mAb attenuated carcinoma cell-mediated polarization of monocytes into M2-like TAMs. These data suggest that anti-AQP3 mAb suppresses tumor growth by attenuating immunosuppressive M2-like TAMs, which in turn maintains the antitumor function of T cells in the TME. Thus, the anti-AQP3 mAb is a potential cancer therapy that functions by targeting TAMs.

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AQP9 transports lactate in tumor-associated macrophages to stimulate an M2-like polarization that promotes colon cancer progression

Yundi Shi, Masato Yasui, Mariko Hara-Chikuma

Biochemistry and Biophysics Reports (Elsevier BV) 31 101317 - 101317 2022.09

Last author, Corresponding author, Accepted, ISSN 2405-5808

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Low humidity altered the gene expression profile of keratinocytes in a three-dimensional skin model

Kenji Shinohara, Mariko Hara-Chikuma

Molecular Biology Reports (Springer Science and Business Media LLC) 49 ( 8 ) 7465 - 7474 2022.05

Last author, Corresponding author, Accepted, ISSN 0301-4851

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Effect of topical application of lipopolysaccharide on contact hypersensitivity

Manami Tanaka, Chie Kohchi, Hiroyuki Inagawa, Takeshi Ikemoto, Mariko Hara-Chikuma

Biochemical and Biophysical Research Communications (Elsevier BV) 586 100 - 106 2022.01

Last author, Corresponding author, Accepted, ISSN 0006-291X

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Goreisan regulates AQP3 expression and improves diarrhea

Kazuhito Murakami, Ichiro Horie, Mariko Hara‐Chikuma, Tomofumi Shimizu, Chinami Matsumoto, Yoichiro Isohama

Traditional & Kampo Medicine (Wiley) 8 ( 1 ) 91 - 99 2021.04

Accepted, ISSN 2053-4515

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Identification of compounds in red wine that effectively upregulate aquaporin-3 as a potential mechanism of enhancement of skin moisturizing

Yumi Nakamura, Takatsugu Tsuchiya, Mariko Hara-Chikuma, Masato Yasui, Yuko Fukui

Biochemistry and Biophysics Reports (Elsevier BV) 24 100864 - 100864 2020.12

Accepted, ISSN 2405-5808

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Inhibition of aquaporin-3 in macrophages by a monoclonal antibody as potential therapy for liver injury

Mariko Hara-Chikuma, Manami Tanaka, Alan S. Verkman, Masato Yasui

Nature Communications (Springer Science and Business Media LLC) 11 ( 1 ) 5666 2020.12

Lead author, Corresponding author, Accepted

<title>Abstract</title>
Aquaporin 3 (AQP3) is a transporter of water, glycerol and hydrogen peroxide (H2O2) that is expressed in various epithelial cells and in macrophages. Here, we developed an anti-AQP3 monoclonal antibody (mAb) that inhibited AQP3-facilitated H2O2 and glycerol transport, and prevented liver injury in experimental animal models. Using AQP3 knockout mice in a model of liver injury and fibrosis produced by CCl4, we obtained evidence for involvement of AQP3 expression in nuclear factor-κB (NF-κB) cell signaling, hepatic oxidative stress and inflammation in macrophages during liver injury. The activated macrophages caused stellate cell activation, leading to liver injury, by a mechanism involving AQP3-mediated H2O2 transport. Administration of an anti-AQP3 mAb, which targeted an extracellular epitope on AQP3, prevented liver injury by inhibition of AQP3-mediated H2O2 transport and macrophage activation. These findings implicate the involvement of macrophage AQP3 in liver injury, and provide evidence for mAb inhibition of AQP3-mediated H2O2 transport as therapy for macrophage-dependent liver injury.

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Involvement of NADPH oxidase 1 in UVB-induced cell signaling and cytotoxicity in human keratinocytes.

Glady A, Tanaka M, Moniaga CS, Yasui M, Hara-Chikuma M

Biochemistry and biophysics reports 14 7 - 15 2018.07

Corresponding author, Accepted

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Transcription Factor MafB Coordinates Epidermal Keratinocyte Differentiation

Masashi Miyai, Michito Hamada, Takashi Moriguchi, Junichiro Hiruma, Akiyo Kamitani-Kawamoto, Hajime Watanabe, Mariko Hara-Chikuma, Kenzo Takahashi, Satoru Takahashi, Kohsuke Kataoka

JOURNAL OF INVESTIGATIVE DERMATOLOGY 136 ( 9 ) 1848 - 1857 2016.09

Accepted, ISSN 0022-202X

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Aquaporin-3 potentiates allergic airway inflammation in ovalbumininduced murine asthma

Kohei Ikezoe, Toru Oga, Tetsuya Honda, Mariko Hara-Chikuma, Xiaojun Ma, Tatsuaki Tsuruyama, Kazuko Uno, Jun-ichi Fuchikami, Kiminobu Tanizawa, Tomohiro Handa, Yoshio Taguchi, Alan S. Verkman, Shuh Narumiya, Michiaki Mishima, Kazuo Chin

SCIENTIFIC REPORTS 6 25781 2016.05

Accepted, ISSN 2045-2322

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Role of mitochondrial hydrogen peroxide induced by intermittent hypoxia in airway epithelial wound repair in vitro

Satoshi Hamada, Atsuyasu Sato, Mariko Hara-Chikuma, Hiroki Satooka, Koichi Hasegawa, Kazuya Tanimura, Kiminobu Tanizawa, Morito Inouchi, Tomohiro Handa, Toru Oga, Shigeo Muro, Michiaki Mishima, Kazuo Chin

EXPERIMENTAL CELL RESEARCH 344 ( 1 ) 143 - 151 2016.05

Accepted, ISSN 0014-4827

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Aquaporin-3 Controls Breast Cancer Cell Migration by Regulating Hydrogen Peroxide Transport and Its Downstream Cell Signaling

Hiroki Satooka, Mariko Hara-Chikuma

MOLECULAR AND CELLULAR BIOLOGY 36 ( 7 ) 1206 - 1218 2016.04

Corresponding author, Accepted, ISSN 0270-7306

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Involvement of aquaporin-3 in epidermal growth factor receptor signaling via hydrogen peroxide transport in cancer cells

Mariko Hara-Chikuma, Sachiko Watanabe, Hiroki Satooka

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 471 ( 4 ) 603 - 609 2016.03

Lead author, Corresponding author, Accepted, ISSN 0006-291X

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Aquaporin-9 facilitates membrane transport of hydrogen peroxide in mammalian cells

Sachiko Watanabe, Catharina Sagita Moniaga, Soren Nielsen, Mariko Hara-Chikuma

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 471 ( 1 ) 191 - 197 2016.02

Corresponding author, Accepted, ISSN 0006-291X

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Aquaporin-9-expressing neutrophils are required for the establishment of contact hypersensitivity

Catharina Sagita Moniaga, Sachiko Watanabe, Tetsuya Honda, Soren Nielsen, Mariko Hara-Chikuma

SCIENTIFIC REPORTS 5 15319 2015.10

Corresponding author, Accepted, ISSN 2045-2322

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Aquaporin-3-mediated hydrogen peroxide transport is required for NF-kappa B signalling in keratinocytes and development of psoriasis

Mariko Hara-Chikuma, Hiroki Satooka, Sachiko Watanabe, Tetsuya Honda, Yoshiki Miyachi, Takeshi Watanabe, A. S. Verkman

NATURE COMMUNICATIONS 6 7454 2015.06

Lead author, Corresponding author, Accepted, ISSN 2041-1723

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Protease Activity Enhances Production of Thymic Stromal Lymphopoietin and Basophil Accumulation in Flaky Tail Mice

Catharina S. Moniaga, Se Kyoo Jeong, Gyohei Egawa, Saeko Nakajima, Mariko Hara-Chikuma, Jeong Eun Jeon, Seung Hun Lee, Toshihiko Hibino, Yoshiki Miyachi, Kenji Kabashima

AMERICAN JOURNAL OF PATHOLOGY 182 ( 3 ) 841 - 851 2013.03

Accepted, ISSN 0002-9440

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Chemokine-dependent T cell migration requires aquaporin-3-mediated hydrogen peroxide uptake

Mariko Hara-Chikuma, Shunsuke Chikuma, Yoshinori Sugiyama, Kenji Kabashima, Alan S. Verkman, Shintaro Inoue, Yoshiki Miyachi

JOURNAL OF EXPERIMENTAL MEDICINE 209 ( 10 ) 1743 - 1752 2012.09

Lead author, Corresponding author, Accepted, ISSN 0022-1007

Langerhans cells are critical in epicutaneous sensitization with protein antigen via thymic stromal lymphopoietin receptor signaling

Saeko Nakajima, Botond Z. Igyarto, Tetsuya Honda, Gyohei Egawa, Atsushi Otsuka, Mariko Hara-Chikuma, Norihiko Watanabe, Steven F. Ziegler, Michio Tomura, Kayo Inaba, Yoshiki Miyachi, Daniel H. Kaplan, Kenji Kabashima

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY 129 ( 4 ) 1048 - U564 2012.04

Accepted, ISSN 0091-6749

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Involvement of aquaporin-7 in the cutaneous primary immune response through modulation of antigen uptake and migration in dendritic cells

Mariko Hara-Chikuma, Yoshinori Sugiyama, Kenji Kabashima, Eisei Sohara, Shinichi Uchida, Sei Sasaki, Shintaro Inoue, Yoshiki Miyachi

FASEB JOURNAL 26 ( 1 ) 211 - 218 2012.01

Lead author, Corresponding author, Accepted, ISSN 0892-6638

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Upregulation of Aquaporin-3 Is Involved in Keratinocyte Proliferation and Epidermal Hyperplasia

Kyoko Nakahigashi, Kenji Kabashima, Akihiko Ikoma, Alan S. Verkman, Yoshiki Miyachi, Mariko Hara-Chikuma

JOURNAL OF INVESTIGATIVE DERMATOLOGY 131 ( 4 ) 865 - 873 2011.04

Last author, Corresponding author, Accepted, ISSN 0022-202X

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Flaky Tail Mouse Denotes Human Atopic Dermatitis in the Steady State and by Topical Application with Dermatophagoides pteronyssinus Extract

Catharina Sagita Moniaga, Gyohei Egawa, Hiroshi Kawasaki, Mariko Hara-Chikuma, Tetsuya Honda, Hideaki Tanizaki, Saeko Nakajima, Atsushi Otsuka, Hiroyuki Matsuoka, Akiharu Kubo, Jun-ichi Sakabe, Yoshiki Tokura, Yoshiki Miyachi, Masayuki Amagai, Kenji Kabashima

AMERICAN JOURNAL OF PATHOLOGY 176 ( 5 ) 2385 - 2393 2010.05

Accepted, ISSN 0002-9440

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The expression of differentiation markers in aquaporin-3 deficient epidermis

Mariko Hara-Chikuma, Kenzo Takahashi, Shunsuke Chikuma, A. S. Verkman, Yoshiki Miyachi

ARCHIVES OF DERMATOLOGICAL RESEARCH 301 ( 3 ) 245 - 252 2009.03

Lead author, Corresponding author, Accepted, ISSN 0340-3696

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Roles of aquaporin-3 in the epidermis

Mariko Hara-Chikuma, A. S. Verkman

JOURNAL OF INVESTIGATIVE DERMATOLOGY 128 ( 9 ) 2145 - 2151 2008.09

Lead author, Accepted, ISSN 0022-202X

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Aberrant aquaporin 5 expression in the sweat gland in aquagenic wrinkling of the palms

Kenji Kabashima, Takatoshi Shimauchi, Miwa Kobayashi, Shoko Fukamachi, Chika Kawakamia, Makiko Ogata, Rieko Kabashima, Tomoko Mori, Tomoko Ota, Satoshi Fukushima, Mariko Hara-Chikuma, Yoshiki Tokura

JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY 59 ( 2 ) S28 - S32 2008.08

Accepted, ISSN 0190-9622

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Aquaporins - new players in cancer biology

A. S. Verkman, Mariko Hara-Chikuma, Marios C. Papadopoulos

JOURNAL OF MOLECULAR MEDICINE-JMM 86 ( 5 ) 523 - 529 2008.05

Accepted, ISSN 0946-2716

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Aquaporin-3 facilitates epidermal cell migration and proliferation during wound healing

Mariko Hara-Chikuma, A. S. Verkman

JOURNAL OF MOLECULAR MEDICINE-JMM 86 ( 2 ) 221 - 231 2008.02

Lead author, Accepted, ISSN 0946-2716

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Prevention of skin tumorigenesis and impairment of epidermal cell proliferation by targeted aquaporin-3 gene disruption

Mariko Hara-Chikuma, A. S. Verkman

MOLECULAR AND CELLULAR BIOLOGY 28 ( 1 ) 326 - 332 2008.01

Lead author, Accepted, ISSN 0270-7306

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Physiological roles of glycerol-transporting aquaporins: the aquaglyceroporins

M Hara-Chikuma, AS Verkman

CELLULAR AND MOLECULAR LIFE SCIENCES 63 ( 12 ) 1386 - 1392 2006.06

Lead author, Accepted, ISSN 1420-682X

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Aquaporin-1 facilitates epithelial cell migration in kidney proximal tubule

Mariko Hara-Chikuma, A. S. Verkman

JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY 17 ( 1 ) 39 - 45 2006.01

Lead author, Accepted, ISSN 1046-6673

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Disruption of aquaporin-11 produces polycystic kidneys following vacuolization of the proximal tubule

Y Morishita, T Matsuzaki, M Hara-Chikuma, A Andoo, M Shimono, A Matsuki, K Kobayashi, M Ikeda, T Yamamoto, A Verkman, E Kusano, S Ookawara, K Takata, S Sasaki, K Ishibashi

MOLECULAR AND CELLULAR BIOLOGY 25 ( 17 ) 7770 - 7779 2005.09

Accepted, ISSN 0270-7306

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Aquaporin-3 functions as a glycerol transporter in mammalian skin

M Hara-Chikuma, AS Verkman

BIOLOGY OF THE CELL 97 ( 7 ) 479 - 486 2005.07

Lead author, Accepted, ISSN 0248-4900

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Anti-obese action of raspberry ketone

C Morimoto, Y Satoh, M Hara, S Inoue, T Tsujita, H Okuda

LIFE SCIENCES 77 ( 2 ) 194 - 204 2005.05

Accepted, ISSN 0024-3205

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Impaired acidification in early endosomes of CIC-5 deficient proximal tubule

M Hara-Chikuma, YH Wang, SE Guggino, WB Guggino, AS Verkman

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 329 ( 3 ) 941 - 946 2005.04

Lead author, Accepted, ISSN 0006-291X

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Progressive adipocyte hypertrophy in aquaporin-7-deficient mice - Adipocyte glycerol permeability as a novel regulator of fat accumulation

M Hara-Chikuma, E Sohara, T Rai, M Ikawa, M Okabe, S Sasaki, S Uchida, AS Verkman

JOURNAL OF BIOLOGICAL CHEMISTRY 280 ( 16 ) 15493 - 15496 2005.04

Lead author, Accepted, ISSN 0021-9258

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Impairment of angiogenesis and cell migration by targeted aquaporin-1 gene disruption

S Saadoun, MC Papadopoulos, M Hara-Chikuma, AS Verkman

NATURE 434 ( 7034 ) 786 - 792 2005.04

Accepted, ISSN 0028-0836

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ClC-3 chloride channels facilitate endosomal acidification and chloride accumulation

M Hara-Chikuma, BX Yang, ND Sonawane, S Sasaki, S Uchida, AS Verkman

JOURNAL OF BIOLOGICAL CHEMISTRY 280 ( 2 ) 1241 - 1247 2005.01

Lead author, Accepted, ISSN 0021-9258

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Epidermal-specific defect of GPI anchor in Pig-a null mice results in harlequin ichthyosis-like features

M Hara-Chikuma, J Takeda, M Tarutani, Y Uchida, WM Holleran, Y Endo, PM Elias, S Inoue

JOURNAL OF INVESTIGATIVE DERMATOLOGY 123 ( 3 ) 464 - 469 2004.09

Lead author, Accepted, ISSN 0022-202X

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Alteration of the 4-sphingenine scaffolds of ceramides in keratinocyte-specific Arnt-deficient mice affects skin barrier function

S Takagi, H Tojo, S Tomita, S Sano, S Itami, M Hara, S Inoue, K Horie, G Kondoh, K Hosokawa, FJ Gonzalez, J Takeda

JOURNAL OF CLINICAL INVESTIGATION 112 ( 9 ) 1372 - 1382 2003.11

Accepted, ISSN 0021-9738

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Glycerol replacement corrects defective skin hydration, elasticity, and barrier function in aquaporin-3-deficient mice

M Hara, AS Verkman

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 100 ( 12 ) 7360 - 7365 2003.06

Lead author, Accepted, ISSN 0027-8424

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Design, synthesis, and evaluation of beta-galactosylceramide mimics promoting beta-glucocerebrosidase activity in keratinocytes

K Fukunaga, M Yoshida, F Nakajima, R Uematsu, M Hara, S Inoue, H Kondo, SI Nishimura

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS 13 ( 5 ) 813 - 815 2003.03

Accepted, ISSN 0960-894X

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Selectively reduced glycerol in skin of aquaporin-3-deficient mice may account for impaired skin hydration, elasticity, and barrier recovery

M Hara, TH Ma, AS Verkman

JOURNAL OF BIOLOGICAL CHEMISTRY 277 ( 48 ) 46616 - 46621 2002.11

Lead author, Accepted, ISSN 0021-9258

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Human epidermal glucosylceramides are major precursors of stratum corneum ceramides

S Hamanaka, M Hara, H Nishio, F Otsuka, A Suzuki, Y Uchida

JOURNAL OF INVESTIGATIVE DERMATOLOGY 119 ( 2 ) 416 - 423 2002.08

Lead author, Accepted, ISSN 0022-202X

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Rapid compensation for glycosylphosphatidylinositol anchor deficient keratinocytes after birth: Visualization of glycosylphosphatidylinositol-anchored proteins in situ

XH Gao, G Kondoh, M Tarutani, M Hara, S Inoue, T Nakanishi, M Okabe, Y Yamaguchi, K Yoshikawa, S Itami, J Takeda

JOURNAL OF INVESTIGATIVE DERMATOLOGY 118 ( 6 ) 998 - 1002 2002.06

Accepted, ISSN 0022-202X

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Impaired stratum corneum hydration in mice lacking epidermal water channel aquaporin-3

TH Ma, M Hara, R Sougrat, JM Verbavatz, AS Verkman

JOURNAL OF BIOLOGICAL CHEMISTRY 277 ( 19 ) 17147 - 17153 2002.05

Accepted, ISSN 0021-9258

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Osmotic stress up-regulates aquaporin-3 gene expression in cultured human keratinocytes

Y Sugiyama, Y Ota, M Hara, S Inoue

BIOCHIMICA ET BIOPHYSICA ACTA-GENE STRUCTURE AND EXPRESSION 1522 ( 2 ) 82 - 88 2001.12

Accepted, ISSN 0167-4781

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Stratum corneum ceramides: their function and origins

Y Uchida, M Hara, S Hamanaka

SEIKAGAKU 73 ( 4 ) 268 - 272 2001.04

Accepted, ISSN 0037-1017

Epidermal sphingomyelins are precursors for selected stratum corneum ceramides

Y Uchida, M Hara, H Nishio, E Sidransky, S Inoue, F Otsuka, A Suzuki, PM Elias, WM Holleran, S Hamanaka

JOURNAL OF LIPID RESEARCH 41 ( 12 ) 2071 - 2082 2000.12

Accepted, ISSN 0022-2275

Galactocerebroside and not glucocerebroside or ceramide stimulate epidermal beta-glucocerebrosidase activity

M Hara, Y Uchida, A Haratake, K Mimura, S Hamanaka

JOURNAL OF DERMATOLOGICAL SCIENCE 16 ( 2 ) 111 - 119 1998.01

Lead author, Accepted, ISSN 0923-1811

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Structural and biochemical basis for the UVB-induced alterations in epidermal barrier function

WM Holleran, Y Uchida, L HalkierSorensen, A Haratake, M Hara, JH Epstein, PM Elias

PHOTODERMATOLOGY PHOTOIMMUNOLOGY & PHOTOMEDICINE 13 ( 4 ) 117 - 128 1997.08

Accepted, ISSN 0905-4383

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