Updated on 2025/06/25

Information

 

写真a

 
ISHIKAWA MIZUHO
 
Organization
Medical Institute of Bioregulation Department of Molecular and Cellular Biology Assistant Professor
Title
Assistant Professor
Contact information
メールアドレス

Research Areas

  • Life Science / Developmental biology

Degree

  • Ph.D.

Research History

  • Kyushu University Medical Institute of Bioregulation Department of Molecular and Cellular Biology  Assistant Professor 

    2023.9 - Present

  • Kumamoto University IRCMS part-time researcher 

    2022.4 - 2023.8

  • Tottori University 医学部生命科学科 Academic Researcher 

    2021.4 - 2022.3

Education

  • Tottori University   医学系研究科 博士後期課程  

    2018.4 - 2021.3

  • Tottori University   医学系研究科 博士前期課程  

    2016.4 - 2018.3

  • Tottori University   医学部   生命科学科

    2012.4 - 2016.3

Awards

  • 米子医学会賞

    2021.3   鳥取大学   Yonago

  • 令和元年度 鳥取大学医学部 下田光造記念賞

    2020.3  

  • 鳥取大学 医学部 生命科学科 鳥取大学医学部生命科学科特別奨励賞

    2020.1  

  • 第9回RNAi研究会 共催 第4回日本細胞外小胞学会 優秀口頭発表賞

    2017.9  

  • 第25回がん転移学会学術集会・総会 優秀ポスター賞

    2016.7  

  • 第105回日本病理学会総会 学部学生ポスター最優秀賞

    2016.5  

  • 文部科学省 新学術領域研究「がん研究分野の特性等を踏まえた支援活動」平成27年度 個体レベルでのがん研究支援活動ワークショップ 優秀ポスター賞

    2016.2  

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Papers

  • Integrin-Binding Matricellular Protein Fibulin-5 Maintains Epidermal Stem Cell Heterogeneity During Skin Aging

    Wenxin Fan, Mizuho Ishikawa, Erna Raja, Ahmed M. Hegazy, Hinata Date, Yen Xuan Ngo, Yoshifumi Sato, Kazuya Yamagata, Hiromi Yanagisawa, Aiko Sada

    2025.5

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    Publisher:Cold Spring Harbor Laboratory  

    ABSTRACT

    The extracellular matrix (ECM) is crucial in building the extracellular environment and translating extracellular information into biochemical signals that sustain organ functions. Fibulin-5 (Fbln5) is a multifunctional ECM protein essential for forming elastic fibers and regulating cellular functions by binding to integrins. While fibulin-5 expression decreases with age in human skin, the functional implications of this decrease, particularly in epidermal stem cell regulation, have remained largely unexplored. Here, we find that the knocking out ofFbln5in mice results in early impairments of epidermal stem cell properties, similar to the chronological aging of the skin. TheFbln5deficiency suppresses the expression of integrins and other cell junction proteins, leading to the inactivation of YAP signaling in epidermal stem cells. This reduction in YAP signaling results in the downregulation of the fast-cycling epidermal stem cell marker SLC1A3 in human skin and primary keratinocytes. These results suggest that, in addition to its known function in elastic fiber formation, fibulin-5 also plays a critical role in regulating the balance of epidermal stem cell populations during skin aging and coordinating the crosstalk between the extracellular environment and intracellular signaling.

    DOI: 10.1101/2025.05.26.656217

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  • Retinoic acid signaling alters the balance of epidermal stem cell populations in the skin

    Thisakorn Dumrongphuttidecha, Mizuho Ishikawa, Nina Cabezas-Wallscheid, Aiko Sada

    2025.4

  • Defining epithelial stem cell heterogeneity through undulating structures of the skin and oral mucosa

    Mizuho Ishikawa, Yen Xuan Ngo, Ikuto Nishikawa, Hiroko Kato, Ryo Maeda, Ryosuke Mizuno, Jun Mizuno, Kenji Izumi, Hiromi Yanagisawa, Aiko Sada

    2025.1

  • MTA1, a metastasis‑associated protein, in endothelial cells is an essential molecule for angiogenesis. Reviewed International journal

    Mizuho Ishikawa, Mitsuhiko Osaki, Narumi Uno, Takahito Ohira, Hiroyuki Kugoh, Futoshi Okada

    Molecular medicine reports   25 ( 1 )   2022.1

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

    Our previous study revealed that metastasis‑associated protein 1 (MTA1), which is expressed in vascular endothelial cells, acts as a tube formation promoting factor. The present study aimed to clarify the importance of MTA1 expression in tube formation using MTA1‑knockout (KO) endothelial cells (MTA1‑KO MSS31 cells). Tube formation was significantly suppressed in MTA1‑KO MSS31 cells, whereas MTA1‑overexpression MTA1‑KO MSS31 cells regained the ability to form tube‑like structures. In addition, western blotting analysis revealed that MTA1‑KO MSS31 cells showed significantly higher levels of phosphorylation of non‑muscle myosin heavy chain IIa, which resulted in suppression of tube formation. This effect was attributed to a decrease of MTA1/S100 calcium‑binding protein A4 complex formation. Moreover, inhibition of tube formation in MTA1‑KO MSS31 cells could not be rescued by stimulation with vascular endothelial growth factor (VEGF). These results demonstrated that MTA1 may serve as an essential molecule for angiogenesis in endothelial cells and be involved in different steps of the angiogenic process compared with the VEGF/VEGF receptor 2 pathway. The findings showed that endothelial MTA1 and its pathway may serve as promising targets for inhibiting tumor angiogenesis, further supporting the development of MTA1‑based antiangiogenic therapies.

    DOI: 10.3892/mmr.2021.12527

    Repository Public URL: https://hdl.handle.net/2324/7173588

  • ヒト胃癌細胞が分泌するAmigo2包含エクソソームは、胃癌細胞と肝内皮細胞との接着能を亢進させる

    井筒 瑠奈, 鄭 朱蒙パトリック, 根本 英幸, 石川 瑞穂, 尾崎 充彦, 岡田 太

    日本病理学会会誌   110 ( 1 )   373 - 373   2021.3

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    Language:Japanese  

  • Splice variants of lysosome‑associated membrane proteins 2A and 2B are involved in sunitinib resistance in human renal cell carcinoma cells. Reviewed International journal

    Ryoma Nishikawa, Mitsuhiko Osaki, Ryo Sasaki, Mizuho Ishikawa, Tetsuya Yumioka, Noriya Yamaguchi, Hideto Iwamoto, Masashi Honda, Tomohiro Kabuta, Atsushi Takenaka, Futoshi Okada

    Oncology reports   44 ( 5 )   1810 - 1820   2020.9

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

    Sunitinib, a tyrosine kinase inhibitor, is among the first‑line treatments for metastatic or advanced stage renal cell carcinoma (RCC). However, patients with RCC develop resistance to sunitinib. We have previously demonstrated that lysosome‑associated membrane protein 2 (LAMP‑2), which has three splice variants with different functions (LAMP‑2A, LAMP‑2B, and LAMP‑2C), is involved in RCC. In the present study, we examined which splice variants of LAMP‑2 contributed to sunitinib resistance in RCC cells. In vitro analysis using ACHN, human RCC cell line, revealed that the IC50 of sunitinib was significantly increased by overexpression of LAMP‑2A and LAMP‑2B, but not LAMP‑2C (P<0.01). Kaplan‑Meier survival analysis using clinical samples revealed an association between shorter survival and high expression of LAMP‑2A and LAMP‑2B, but not LAMP‑2C, in patients with RCC treated with sunitinib (P=0.01). Furthermore, high expression of LAMP‑2A and LAMP‑2B in RCC revealed a weak to moderate inverse correlation with the tumor shrinkage rate and progression‑free survival, respectively. Thus, high expression of LAMP‑2A and LAMP‑2B contributed to the acquisition of sunitinib resistance, indicating that the expression of these two variants can predict the efficacy of sunitinib treatment in patients with RCC.

    DOI: 10.3892/or.2020.7752

    Repository Public URL: https://hdl.handle.net/2324/7178659

  • Bisphosphonate-induced reactive oxygen species inhibit proliferation and migration of oral fibroblasts: A pathogenesis of bisphosphonate-related osteonecrosis of the jaw. Reviewed International journal

    Naomi Taniguchi, Mitsuhiko Osaki, Kunishige Onuma, Mizuho Ishikawa, Kazuo Ryoke, Isamu Kodani, Futoshi Okada

    Journal of periodontology   91 ( 7 )   947 - 955   2020.7

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

    BACKGROUND: The onset mechanism for bisphosphonate-related osteonecrosis of the jaw (BRONJ) has been reported, with a focus on bone remodeling, biofilm formation, and epithelial cell proliferation and migration. However, the involvement of stromal cells, especially fibroblasts, in the oral cavity is unclear. Therefore, this study was focused on how bisphosphonates (BPs) affect orthotopic periodontal ligament fibroblasts from the viewpoint of oxidative stress compared with ectopically obtained fibroblasts. METHODS: Normal human periodontal ligament fibroblasts (HPdLFs) and normal human dermal fibroblasts (NHDFs) were used to gain insight into the functional differences in sensitivity and reactions to BPs. Cell growth assay, measurement of reactive oxygen species (ROS) and nitric oxide (NO) production, and wound-healing assay in vitro were performed. Maxillary first molars were extracted in C57BL/6 mice and either BP, N-acetyl-cysteine (NAC), and BP or saline were administered. RESULTS: BP-induced IC50 values were significantly lower in HPdLFs (30.6 µM) than in NHDFs (109.7 µM). BP resulted in an increase in ROS, but not NO generation in HPdLFs. BPs also inhibited proliferation and migration of HPdLFs but not NHDFs, while the addition of a ROS inhibitor, NAC, reversed those inhibitions. A BRONJ mouse model in which BP was administered and then the tooth was extracted, impaired wound healing of the socket was observed. When NAC was administered before tooth extraction, wound healing was significantly improved. CONCLUSION: These results suggest that BP causes fibroblasts obtained from the oral cavity but not from skin to generate ROS and that the subsequent ROS-mediated inhibition of fibroblast growth and migration definitely delays wound healing, thereby contributing to BRONJ pathogenesis.

    DOI: 10.1002/JPER.19-0385

    Repository Public URL: https://hdl.handle.net/2324/7178695

  • Correlation of two distinct metastasis-associated proteins, MTA1 and S100A4, in angiogenesis for promoting tumor growth. Reviewed International journal

    Mizuho Ishikawa, Mitsuhiko Osaki, Makoto Yamagishi, Kunishige Onuma, Hisao Ito, Futoshi Okada, Hideya Endo

    Oncogene   38 ( 24 )   4715 - 4728   2019.6

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

    Extensive studies on metastasis-associated proteins, S100A4 and MTA1, have been carried out for over two decades, but correlation of both proteins remains obscure. Here we show evidence for the correlation in angiogenesis. First, silencing of each protein by siRNA-mediated knockdown in mouse endothelial MSS31 cells resulted in the inhibition of tube formation. Unexpectedly, the knockdown of MTA1 affected not only its own expression but also the expression of S100A4, whereas silencing of S100A4 did not affect the MTA1 expression. Additionally, non-muscle myosin IIA (NMIIA) phosphorylation, which was partly controlled by S100A4, was found to be upregulated by knockdown of both proteins in MSS31 cells. Moreover, cycloheximide treatment of MSS31 cells revealed that the rate of S100A4 degradation was accelerated by MTA1 knockdown. This finding, together with our observation that cytoplasmic MTA1, but not nuclear MTA1, was colocalized with S100A4, suggested the involvement of MTA1 in S100A4 stability. The direct in vivo angiogenesis assay showed that both protein siRNAs provoked a significant inhibition of new blood vessel formation induced by angiogenic factors, indicating their anti-angiogenic activities. Treatment of human pancreatic tumor (PANC-1) xenograft in mice with mMTA1 siRNA resulted in tumor regression via suppression of angiogenesis in vivo, as also observed in the case of human prostate cancer xenograft treated with mS100A4 siRNA. Taken together, these data led us to conclude that the MTA1-S100A4-NMIIA axis exists in endothelial cells as a novel pathway in promoting tumor vascular formation and could be a target for suppressing tumor growth and metastasis.

    DOI: 10.1038/s41388-019-0748-z

    Repository Public URL: https://hdl.handle.net/2324/7178658

  • 血管内皮細胞におけるMTA1発現は血管新生阻害の標的分子となりうる(MTA1 expressed in endothelial cells is a candidate target molecule for inhibiting angiogenesis)

    石川 瑞穂, 尾崎 充彦, 山岸 誠, 小沼 邦重, 井藤 久雄, 岡田 太, 遠藤 英也

    日本病理学会会誌   107 ( 1 )   342 - 342   2018.4

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    血管内皮細胞におけるMTA1発現は血管新生阻害の標的分子となりうる(MTA1 expressed in endothelial cells is a candidate target molecule for inhibiting angiogenesis)

    Repository Public URL: https://hdl.handle.net/2324/7237091

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MISC

  • 血管内皮細胞に発現しているMTA1はS100A4を介する事で新たな腫瘍血管新生の阻害標的になりうる

    石川瑞穂, 尾崎充彦, 尾崎充彦, 山岸誠, 小沼邦重, 井藤久雄, 井藤久雄, 岡田太, 岡田太, 遠藤英也

    日本病理学会会誌   2019.4

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    Language:Japanese  

    血管内皮細胞に発現しているMTA1はS100A4を介する事で新たな腫瘍血管新生の阻害標的になりうる

    Repository Public URL: https://hdl.handle.net/2324/7237094

  • 血管内皮細胞におけるMTA1発現の抑制はS100A4発現抑制を介した血管新生阻害による抗腫瘍効果を引き起こす(Silencing of MTA1 in endothelial cells induced anti-tumor effect by inhibiting angiogenesis via downregulation of S100A4)

    石川 瑞穂, 尾崎 充彦, 山岸 誠, 小沼 邦重, 井藤 久雄, 岡田 太, 遠藤 英也

    日本癌学会総会記事   2018.9

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    血管内皮細胞におけるMTA1発現の抑制はS100A4発現抑制を介した血管新生阻害による抗腫瘍効果を引き起こす(Silencing of MTA1 in endothelial cells induced anti-tumor effect by inhibiting angiogenesis via downregulation of S100A4)

    Repository Public URL: https://hdl.handle.net/2324/7237092

  • 血管内皮細胞におけるMTA1発現は血管新生阻害の標的分子となりうる(MTA1 expressed in endothelial cells is a candidate target molecule for inhibiting angiogenesis)

    石川 瑞穂, 尾崎 充彦, 山岸 誠, 小沼 邦重, 井藤 久雄, 岡田 太, 遠藤 英也

    日本病理学会会誌   2018.4

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    Language:English  

    血管内皮細胞におけるMTA1発現は血管新生阻害の標的分子となりうる(MTA1 expressed in endothelial cells is a candidate target molecule for inhibiting angiogenesis)

    Repository Public URL: https://hdl.handle.net/2324/7237094

  • 血管内皮細胞におけるMTA1の抑制はS100A4抑制を介した血管新生阻害による腫瘍退縮を引き起こす

    石川 瑞穂, 尾崎 充彦, 山岸 誠, 小沼 邦重, 井藤 久雄, 岡田 太, 遠藤 英也

    日本癌学会総会記事   2017.9

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    Language:English  

    血管内皮細胞におけるMTA1の抑制はS100A4抑制を介した血管新生阻害による腫瘍退縮を引き起こす

    Repository Public URL: https://hdl.handle.net/2324/7236793

  • 血管内皮細胞におけるMTA1の抑制はS100A4抑制を介した血管新生阻害による腫瘍退縮を引き起こす

    石川 瑞穂, 尾崎 充彦, 山岸 誠, 小沼 邦重, 井藤 久雄, 岡田 太, 遠藤 英也

    日本癌学会総会記事   2016.10

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    Language:English  

    血管内皮細胞におけるMTA1の抑制はS100A4抑制を介した血管新生阻害による腫瘍退縮を引き起こす

    Repository Public URL: https://hdl.handle.net/2324/7236792

  • 血管内皮細胞におけるMTA1発現は血管新生阻害の標的分子となりうる

    石川瑞穂, 尾崎充彦, 尾崎充彦, 平畑美緒, 神田祐介, 津毛美乃里, 山岸誠, 井藤久雄, 井藤久雄, 遠藤英也, 岡田太, 岡田太

    日本病理学会会誌   2016.4

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    血管内皮細胞におけるMTA1発現は血管新生阻害の標的分子となりうる

    Repository Public URL: https://hdl.handle.net/2324/7178696

  • 血管内皮細胞に発現しているMTA1は血管新生阻害の標的分子となりうる

    石川瑞穂, 尾崎充彦, 尾崎充彦, 山岸誠, 岡田太, 岡田太, 遠藤英也

    日本生化学会大会(Web)   2015.12

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    Language:Japanese  

    血管内皮細胞に発現しているMTA1は血管新生阻害の標的分子となりうる

    Repository Public URL: https://hdl.handle.net/2324/7178694

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Professional Memberships

  • 日本がん転移学会

  • 日本癌学会

Academic Activities

  • 幹細胞シンポジウム若手の会

    Role(s): Planning, management, etc.

    2024

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Research Projects

  • 真皮の物理的変化がもたらす表皮リモデリング機構の解明

    2025.4 - 2027.3

    公益財団法人中冨健康科学財団  研究助成金 

    石川瑞穂

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    Authorship:Principal investigator 

  • 真皮の機械物性変化がもたらす皮膚組織ダイナミクスの解明

    2025.4 - 2026.3

    公益財団法人ホーユー科学財団  研究助成 

    石川瑞穂

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    Authorship:Principal investigator  Grant type:Donation

  • 大規模細胞動態解析による培養表皮シートの有効性予測技術の開発

    Grant number:24KK0205  2024.9 - 2027.3

    Grants-in-Aid for Scientific Research  Fund for the Promotion of Joint International Research (International Collaborative Research)

    難波 大輔, 古徳 純一, 上田 敬博, 石川 瑞穂

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    Authorship:Coinvestigator(s)  Grant type:Scientific research funding

    ①海外共同研究先において、ヒト表皮幹細胞を用いて培養表皮シートを作製し、その間の細胞動態をDeepACTによって網羅的に解析する。また日本側において、より大量の細胞を高速に解析できるようにDeepACTの改良を行う。②作製段階で細胞動態解析を行った培養表皮シートを免疫不全マウスに移植し、その組織再生能力を評価する。③移植後の組織再生能力に相関する細胞動態パラメータを同定し、高い組織再生能力を持った培養表皮シートを事前に選別し移植するより優れた重度熱傷治療法を開発する。

    CiNii Research

  • 凹凸構造を模倣した皮膚三次元培養系による皮膚再建に向けたアプローチ

    2024

    株式会社池田理化・株式会社リバネス  第11回池田理化賞 奨励賞 

    石川瑞穂

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    Authorship:Principal investigator  Grant type:Donation

  • Towards an understanding of aging: focusing on the epidermal-dermal network generated by fibroblast diversity

    Grant number:23K14198  2023 - 2025

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Early-Career Scientists

    石川 瑞穂

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    Authorship:Principal investigator  Grant type:Scientific research funding

    線維芽細胞は、組織幹細胞ニッチとして働く細胞の一種で、組織恒常性維持や再生に重要な役割を果たす。近年の研究から、線維芽細胞が非常に豊かな多様性に富むことが明らかになりつつあるが、異なる線維芽細胞集団が存在することの生物学的意義は不明である。申請者はDNA損傷に起因する皮膚老化の原因が表皮幹細胞自体ではなく、そのニッチとして働く線維芽細胞亜集団にあるのではと考え、細胞種特異的なDNA損傷が誘導可能なマウスモデルや空間的トランスクリプトーム解析により正常または老化ストレス環境下での多様な線維芽細胞集団が持つ機能の解明および表皮―真皮ネットワークを基軸とした皮膚老化メカニズムの理解を目指す。

    CiNii Research

  • 「幹細胞ニッチ」としての血管:血管を介した表皮幹細胞制御メカニズムの解明

    2023

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    Authorship:Principal investigator  Grant type:Donation

  • MTA1-S100A4相互作用を標的とした新規血管新生阻害剤の探索

    Grant number:20J11378  2020 - 2021

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for JSPS Fellows

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    Authorship:Principal investigator  Grant type:Scientific research funding

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