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The study on interstitial multicellular crosstalk; Significance of blood and lymphatic vessels.

Planned Research

Project AreaInterstitial literacy: Integrated understanding of disease pathogenesis based on interstitial cell diversity.
Project/Area Number 22H05063
Research Category

Grant-in-Aid for Transformative Research Areas (B)

Allocation TypeSingle-year Grants
Review Section Transformative Research Areas, Section (III)
Research InstitutionKanazawa University

Principal Investigator

Naito Hisamichi  金沢大学, 医学系, 教授 (30570676)

Co-Investigator(Kenkyū-buntansha) 田井 育江  慶應義塾大学, 医学部(信濃町), 講師 (90749508)
Project Period (FY) 2022-05-20 – 2025-03-31
Project Status Completed (Fiscal Year 2024)
Budget Amount *help
¥31,980,000 (Direct Cost: ¥24,600,000、Indirect Cost: ¥7,380,000)
Fiscal Year 2024: ¥10,660,000 (Direct Cost: ¥8,200,000、Indirect Cost: ¥2,460,000)
Fiscal Year 2023: ¥10,660,000 (Direct Cost: ¥8,200,000、Indirect Cost: ¥2,460,000)
Fiscal Year 2022: ¥10,660,000 (Direct Cost: ¥8,200,000、Indirect Cost: ¥2,460,000)
Keywords間質性細胞 / 血管 / リンパ管 / 多細胞間クロストーク / 血管内皮細胞 / マクロファージ / 腸 / 恒常性
Outline of Research at the Start

全身の組織及び臓器は、機能の中心を担う実質細胞と、実質細胞を支持する間質に存在する様々な種類の細胞(間質性細胞)で構成される。これまで様々な生命現象や疾患病態は、実質細胞の機能を主体に理解され、実質細胞との関係性という観点から間質性細胞の意義は見出されてきた。本研究では間質性細胞に焦点を当て、複数の間質性細胞が織りなす多細胞間クロストークを解明することで、間質性細胞の活動が生命現象に及ぼすインパクトを解明する。1細胞解析、3次元イメージングなど最先端の解析手法を駆使して、間質性細胞の重要な構成要素である血管・リンパ管に着目し腸を解析対象として、間質性多細胞間クロストークが持つ意義を解明する。

Outline of Final Research Achievements

Tissues and organs of the body are composed of parenchymal cells, which perform the primary functions, and various types of stromal cells in the interstitium that support those parenchymal cells. In this study, we hypothesize that, rather than parenchymal cells, stromal cells play a central role in both the maintenance of tissue homeostasis and disease pathogenesis. We conducted research using multiple tissues and pathological models, including the intestine. Specifically, in mouse experiments, we generated inflammatory and tumor models. We performed single-cell analysis and three-dimensional imaging to analyze stromal cell function, focusing on cell-cell interaction signals and elucidated the roles of blood vessels and lymphatic vessels in physiological processes and disease states.

Academic Significance and Societal Importance of the Research Achievements

これまで間質性細胞を標的として、生命現象や疾患病態を理解する研究は限られていた。本研究では血管とリンパ管を含む間質性細胞の機能解析に取り組んだ。特に単一の間質性細胞を理解するのではなく、複数の細胞種を包括的に理解するという点は、本研究の独自性であり学術的に意義がある。腸管における炎症と腫瘍の制御機構の理解だけでなく、肝臓の発生過程、肝疾患の形成過程、大動脈疾患の病態形成過程にまで間質性細胞の解析を応用して、生理現象と病態の理解に取り組んだ。将来的には、実質細胞だけでなく間質性細胞を制御することで、様々な疾患を制御できる可能性がある。

Report

(4 results)
  • 2024 Annual Research Report   Final Research Report ( PDF )
  • 2023 Annual Research Report
  • 2022 Annual Research Report
  • Research Products

    (39 results)

All 2025 2024 2023 2022 Other

All Journal Article (12 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 10 results,  Open Access: 10 results) Presentation (17 results) (of which Invited: 9 results) Book (3 results) Remarks (7 results)

  • [Journal Article] Endothelial cell specific LAT1 ablation normalizes tumor vasculature2024

    • Author(s)
      Suehiro Jun-ichi、Kimura Toru、Fukutomi Toshiyuki、Naito Hisamichi、Kanki Yasuharu、Wada Youichiro、Kubota Yoshiaki、Takakura Nobuyuki、Sakurai Hiroyuki
    • Journal Title

      JCI Insight

      Volume: 9 Issue: 18

    • DOI

      10.1172/jci.insight.171371

    • Related Report
      2024 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Metformin synergizes with PD-1 blockade to promote normalization of tumor vessels via CD8T cells and IFNγ2024

    • Author(s)
      Tokumasu Miho、Nishida Mikako、Zhao Weiyang、Chao Ruoyu、Imano Natsumi、Yamashita Nahoko、Hida Kyoko、Naito Hisamichi、Udono Heiichiro
    • Journal Title

      Proceedings of the National Academy of Sciences

      Volume: 121 Issue: 30

    • DOI

      10.1073/pnas.2404778121

    • Related Report
      2024 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] シングルセル解析による血管内皮細胞の細胞多様性解析2024

    • Author(s)
      射場智大、内藤尚道
    • Journal Title

      医学のあゆみ「血管・リンパ管研究の最前線と治療への展開」

      Volume: 289 Pages: 1008-1012

    • Related Report
      2024 Annual Research Report
  • [Journal Article] がん微小環境とがん免疫 がん微小環境における腫瘍血管内皮細胞の異常と細胞多様性2024

    • Author(s)
      内藤尚道
    • Journal Title

      月刊臨床免疫・アレルギー科

      Volume: 82 Pages: 487-494

    • Related Report
      2024 Annual Research Report
  • [Journal Article] ABCG2-Expressing Clonal Repopulating Endothelial Cells Serve to Form and Maintain Blood Vessels2024

    • Author(s)
      Lin Y., Gil CH., Banno K., Yokoyama M., Wingo M., Go E., Prasain N., Liu Y., Hato T., Naito H., Wakabayashi T., Sominskaia M., Gao M., Chen K., Geng F., Gomez Salinero JM., Chen S., Shelley WC., Yoshimoto M., Li Calzi S., Murphy MP., Horie K., Grant MB., Schreiner R., Redmond D., Basile DP., Rafii S
    • Journal Title

      Circulation

      Volume: 150 Issue: 6 Pages: 451-465

    • DOI

      10.1161/circulationaha.122.061833

    • Related Report
      2024 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Diabetes Accelerates Steatohepatitis in Mice2024

    • Author(s)
      Abuduyimiti Tuerdiguli、Goto Hisanori、Kimura Kumi、Oshima Yu、Tanida Ryota、Kamoshita Kyoko、Leerach Nontaphat、Abuduwaili Halimulati、Oo Hein Ko、Li Qifang、Galicia-Medina Cynthia M.、Takayama Hiroaki、Ishii Kiyo-aki、Nakano Yujiro、Takeshita Yumie、Takamura Toshinari、5others
    • Journal Title

      The American Journal of Pathology

      Volume: 194 Issue: 5 Pages: 693-707

    • DOI

      10.1016/j.ajpath.2024.01.007

    • Related Report
      2024 Annual Research Report 2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Aging impairs the ability of vascular endothelial stem cells to generate endothelial cells in mice2023

    • Author(s)
      Shota Shimizu, Tomohiro Iba, Hisamichi Naito, Fitriana Nur Rahmawati, Hirotaka Konishi, Weizhen Jia, Fumitaka Muramatsu, Nobuyuki Takakura
    • Journal Title

      Angiogenesis

      Volume: 26 Issue: 4 Pages: 567-580

    • DOI

      10.1007/s10456-023-09891-8

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Collagen XVII regulates tumor growth in pancreatic cancer through interaction with the tumor microenvironment2023

    • Author(s)
      Kashiwagi Ryosuke、Funayama Ryo、Aoki Shuichi、Matsui Aya、Klein Sebastian、Sato Yukihiro、Suzuki Tsubasa、Murakami Keigo、Inoue Koetsu、Iseki Masahiro、Masuda Kunihiro、Mizuma Masamichi、Naito Hisamichi、Duda Dan G.、Unno Michiaki、Nakayama Keiko
    • Journal Title

      Cancer Science

      Volume: 114 Issue: 11 Pages: 4286-4298

    • DOI

      10.1111/cas.15952

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Single-cell sequencing reveals the existence of fetal vascular endothelial stem cell-like cells in mouse liver2023

    • Author(s)
      Fitriana Nur Rahmawati, Tomohiro Iba, Hisamichi Naito, Shota Shimizu, Hirotaka Konishi, Weizhen Jia, Nobuyuki Takakura
    • Journal Title

      Stem Cell Research & Therapy

      Volume: 14 Issue: 1 Pages: 227-227

    • DOI

      10.1186/s13287-023-03460-y

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Viral uptake and pathophysiology of the lung endothelial cells in age‐associated severe SARS‐CoV‐2 infection models2023

    • Author(s)
      Tsumita Takuya、Iimura Tadahiro、Sawa Hirofumi、Hida Kyoko et al.
    • Journal Title

      Aging Cell

      Volume: 23 Issue: 2

    • DOI

      10.1111/acel.14050

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cellular heterogeneity and stem cells of vascular endothelial cells in blood vessel formation and homeostasis: Insights from single-cell RNA sequencing.2023

    • Author(s)
      Taku Wakabayashi,Hisamichi Naito
    • Journal Title

      Frontiers in cell and developmental biology

      Volume: 11 Pages: 1146399-1146399

    • DOI

      10.3389/fcell.2023.1146399

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] L-carnitine prevents lenvatinib-induced muscle toxicity without impairment of the anti-angiogenic efficacy2023

    • Author(s)
      Zheng Jing,Tomohiro Iba,Hisamichi Naito,Pingping Xu,Jun-Ichi Morishige,Naoto Nagata,Hironao Okubo,Hitoshi Ando
    • Journal Title

      Frontiers in pharmacology

      Volume: 14 Pages: 1182788-1182788

    • DOI

      10.3389/fphar.2023.1182788

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 血管内皮細胞の解析による大動脈疾患の病態解明2025

    • Author(s)
      内藤尚道
    • Organizer
      第54回日本心脈管作動物質学会
    • Related Report
      2024 Annual Research Report
    • Invited
  • [Presentation] Single-cell RNA-seq analysis of adventitial vasa vasorum in human acute aortic syndrome2025

    • Author(s)
      射場智大、吉岡和晃、伊藤行信、平野理恵、藤村聡、田中里佳、前田大地、安藤仁、内藤尚道
    • Organizer
      APPW2025
    • Related Report
      2024 Annual Research Report
  • [Presentation] Single-cell RNA-seq analysis of adventitial vasa vasorum in human acute aortic syndrome2025

    • Author(s)
      吉岡 和晃, 飯野 賢治, 伊藤 行信, 松山 智亮, 小林 奏楽, Beta C. Harlyjoy, 松居 彩, 安藤 仁, 内藤 尚道
    • Organizer
      APPW2025
    • Related Report
      2024 Annual Research Report
  • [Presentation] Liver Sinusoidal Vasculature Remodels During the Perinatal Period2025

    • Author(s)
      Beta C. Harlyjoy, Tomohiro Iba, Aya Matsui, Kazuaki Yoshioka, Hisamichi Naito
    • Organizer
      APPW2025
    • Related Report
      2024 Annual Research Report
  • [Presentation] Unraveling Aortic Disease Mechanisms through Endothelial Cell Analysis in the Vascular Wall2025

    • Author(s)
      内藤尚道
    • Organizer
      第89回日本循環器学会学術集会
    • Related Report
      2024 Annual Research Report
    • Invited
  • [Presentation] ヒト大動脈におけるCD163陽性マクロファージの病態生理的役割2024

    • Author(s)
      松山 智亮、吉岡 和晃、飯野 賢治、射場 智大、松居 彩、竹村 博文、伊藤行信、前田大地、内藤 尚道
    • Organizer
      日本生化学会北陸支部第42回大会
    • Related Report
      2024 Annual Research Report
  • [Presentation] 血管を標的とした細胞分離とシングルセル解析2024

    • Author(s)
      内藤尚道
    • Organizer
      NGS EXPO 2024
    • Related Report
      2024 Annual Research Report
    • Invited
  • [Presentation] 下肢切断を伴う重症下肢虚血患者の毛細血管は断片化と血管新生シグナルの異常を生じる2024

    • Author(s)
      射場 智大, 吉岡 和晃, 安藤 仁, 田中理佳, 内藤 尚道
    • Organizer
      第97回日本生化学会大会
    • Related Report
      2024 Annual Research Report
  • [Presentation] Liver Sinusoidal Vascular Structure is Formed After Birth2024

    • Author(s)
      Beta C. Harlyjoy , Tomohiro Iba , Aya Matsui , Kazuaki Yoshioka, Hisamichi Naito
    • Organizer
      CVMW2024
    • Related Report
      2024 Annual Research Report
  • [Presentation] Exploring the Synergy Between CD157 Positive Liver Endothelial Cells and Human MSCs in Promoting Angiogenesis2024

    • Author(s)
      Yeoreum Jeong, Beta C. Harlyjoy, Kazuaki Yoshioka, Aya Matsui, Hye Ji Lim, Eunji Lee, Jaewoo Choi, Woong Bi Jang, Hisamichi Naito, Sang-mo Kwo
    • Organizer
      CVMW2024
    • Related Report
      2024 Annual Research Report
  • [Presentation] 下肢虚血モデルマウスを用いた血管修復の経時的解析2024

    • Author(s)
      射場 智大, 吉岡 和晃, 若林 卓, 安藤 仁, 内藤 尚道
    • Organizer
      第32回日本血管生物医学会学術集会
    • Related Report
      2024 Annual Research Report
  • [Presentation] 血管新生の経時的解析と疾患病態の理解への応用2024

    • Author(s)
      内藤尚道
    • Organizer
      第49回日本微小循環学会総会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] 血管内皮細胞の細胞多様性と大動脈疾患の病態解明への応用2023

    • Author(s)
      内藤尚道
    • Organizer
      第64回日本脈管学会学術総会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] Analysis of endothelial cell heterogeneity in the tumor microenvironment at single cell resolution2023

    • Author(s)
      内藤尚道
    • Organizer
      第82回日本癌学会学術総会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] シングルセル解析を応用した血管内皮細胞の細胞多様性の理解と血管研究2023

    • Author(s)
      内藤尚道
    • Organizer
      第65回日本平滑筋学会総会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] Vascular Endothelial Cell Heterogeneity and Mechanism of Vascular Formation2023

    • Author(s)
      内藤尚道
    • Organizer
      第100回日本生理学会大会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] 1細胞遺伝子発現解析を応用した血管新生の理解2022

    • Author(s)
      内藤尚道
    • Organizer
      CVMW2022 心血管代謝週間
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Book] もっとよくわかる!線維化と疾患(血管内皮細胞)2023

    • Author(s)
      菅波 孝祥、田中 都、伊藤 美智子(分担執筆 内藤尚道)
    • Total Pages
      172
    • Publisher
      羊土社
    • ISBN
      9784758122139
    • Related Report
      2023 Annual Research Report
  • [Book] 組織恒常性維持における血管の新たな役割2023

    • Author(s)
      松居彩, 内藤尚道
    • Total Pages
      86
    • Publisher
      炎症と免疫(先端医学社)
    • Related Report
      2022 Annual Research Report
  • [Book] 血管系の幹・前駆細胞2022

    • Author(s)
      内藤尚道, 松居彩, 射場智大
    • Total Pages
      98
    • Publisher
      生体の科学(医学書院)
    • Related Report
      2022 Annual Research Report
  • [Remarks] 金沢大学血管分子生理学ホームページ

    • URL

      https://vm-physiol1.w3.kanazawa-u.ac.jp

    • Related Report
      2024 Annual Research Report
  • [Remarks] Researchmap

    • URL

      https://researchmap.jp/hisa_naito

    • Related Report
      2024 Annual Research Report 2023 Annual Research Report
  • [Remarks] 金沢大学ホームページ研究者紹介

    • URL

      https://ridb.kanazawa-u.ac.jp/public/detail.php?id=11315

    • Related Report
      2024 Annual Research Report
  • [Remarks] 金沢大学医薬科学類ホームページ血管分子生理学

    • URL

      https://iyakukagaku.w3.kanazawa-u.ac.jp/news/content/course1-9/

    • Related Report
      2024 Annual Research Report
  • [Remarks] 金沢大学医薬科学類ホームページ血管分子生理学研究紹介動画YouTube

    • URL

      https://youtu.be/KJH9D8Nq8Nc

    • Related Report
      2024 Annual Research Report
  • [Remarks] 金沢大学血管分子生理学

    • URL

      https://vm-physiol1.w3.kanazawa-u.ac.jp/

    • Related Report
      2023 Annual Research Report
  • [Remarks] 金沢大学医薬保健研究域医学系・血管分子生理学

    • URL

      https://vm-physiol1.w3.kanazawa-u.ac.jp/

    • Related Report
      2022 Annual Research Report

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Published: 2022-05-25   Modified: 2026-01-16  

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