Comprehensive Fundamental Research on the Onset and Development of Pneumoconiosis Using TAS-Seq

• Project/Area Number: 20K08556
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53030:Respiratory medicine-related
• Research Institution: Japan Organization of Occupational Health and Safety Japan Bioassay Research Center
• Principal Investigator: Yamano Shotaro 独立行政法人労働者健康安全機構 日本バイオアッセイ研究センター(試験管理部、病理検査部), その他部局等, 室長補佐 (80614528)
• Co-Investigator(Kenkyū-buntansha): 杉原 英志 藤田医科大学, オープンファシリティセンター, 准教授 (50464996) ; 七野 成之 東京理科大学, 研究推進機構生命医科学研究所, 助教 (70822435)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2022: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2021: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2020: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: じん肺 / シングルセル解析 / scRNAseq / インジウム / SITO / シリカ / RCS / 職業性疾患 / 塵肺 / 結晶質シリカ / 酸化インジウムスズ / TAS-Seq / 呼吸器疾患 / 肺疾患 / 肺胞蛋白症 / 肺線維化 / 肺線維症 / 肺がん / 病理

Outline of Research at the Start

じん肺は粉じんによって誘発される日本最大の職業性肺疾患であり、肺線維症のみならず肺がんを合併する事が問題となっている。
本研究では、高感度シングルセル解析技術を駆使し、じん肺の各病態発症-進展過程における構成細胞と異常な細胞間コミュニケーションの特定を時空間軸に沿って俯瞰的に明らかにする。
じん肺発症-進展機構の一端を明らかにし、労働安全衛生に資するじん肺の基盤的な研究成果を提供したい。。

Outline of Final Research Achievements

The identification of pneumoconiosis risk substances and the elucidation of their pathogenic mechanisms and the development of rapid and efficient short-term evaluation methods in an organic manner are urgent issues and important research subjects to be promoted. Therefore, in this study, we generated rat pneumoconiosis by injecting Silica or SITO into rats and performed TAS-Seq analysis to analyze the pathogenesis of pneumoconiosis at a single-cell resolution. As a result, we succeeded in identifying characteristic new cell subsets that constitute pneumoconiosis onset and progression. The clarification of the functions and regulatory mechanisms of these cell groups is expected to accelerate fundamental research on pneumoconiosis that will contribute to occupational safety and health in the future.

Academic Significance and Societal Importance of the Research Achievements

研究開発が遅れている職業性呼吸器疾患の病態解明に対して、疾患の発症・進展に重要な役割を担う可能性のある新規細胞種を同定することができ、学術的意義の高い成果が得られた。加えて、これらの特徴的な細胞に対して介入方法を将来検討できるようになり、職業性肺疾患罹患者の予防、治療等に資する基盤的成果が提供できた。

Research Products

• [Journal Article] Mechanisms of pulmonary disease in F344 rats after workplace-relevant inhalation exposure to cross-linked water-soluble acrylic acid polymers (2023)
  • Author(s): Yamano Shotaro、Takeda Tomoki、Goto Yuko、Hirai Shigeyuki、Furukawa Yusuke、Kikuchi Yoshinori、Misumi Kyohei、Suzuki Masaaki、Takanobu Kenji、Senoh Hideki、Saito Misae、Kondo Hitomi、Kobashi Yoichiro、Okamoto Kenzo、Kishimoto Takumi、Umeda Yumi
  • Journal Title: Respiratory Research Volume: 24 Issue: 1
  • DOI: 10.1186/s12931-023-02355-z
  • Peer Reviewed / Open Access
• [Journal Article] Carcinogenicity and testicular toxicity of 2-bromopropane in a 26-week inhalation study using the rasH2 mouse model (2023)
  • Author(s): Goto Yuko、Saito Arata、Takanobu Kenji、Senoh Hideki、Saito Misae、Umeda Yumi、Yamano Shotaro
  • Journal Title: Scientific Reports Volume: 13 Issue: 1
  • DOI: 10.1038/s41598-023-28825-4
  • Peer Reviewed / Open Access
• [Journal Article] Pulmonary dust foci as rat pneumoconiosis lesion induced by titanium dioxide nanoparticles in 13-week inhalation study (2022)
  • Author(s): Yamano Shotaro、Goto Yuko、Takeda Tomoki、Hirai Shigeyuki、Furukawa Yusuke、Kikuchi Yoshinori、Kasai Tatsuya、Misumi Kyohei、Suzuki Masaaki、Takanobu Kenji、Senoh Hideki、Saito Misae、Kondo Hitomi、Umeda Yumi
  • Journal Title: Particle and Fibre Toxicology Volume: 19 Issue: 1
  • DOI: 10.1186/s12989-022-00498-3
  • Peer Reviewed / Open Access
• [Journal Article] No evidence for carcinogenicity of titanium dioxide nanoparticles in 26-week inhalation study in rasH2 mouse model (2022)
  • Author(s): Yamano Shotaro、Takeda Tomoki、Goto Yuko、Hirai Shigeyuki、Furukawa Yusuke、Kikuchi Yoshinori、Kasai Tatsuya、Misumi Kyohei、Suzuki Masaaki、Takanobu Kenji、Senoh Hideki、Saito Misae、Kondo Hitomi、Umeda Yumi
  • Journal Title: Scientific Reports Volume: 12 Issue: 1
  • DOI: 10.1038/s41598-022-19139-y
  • Peer Reviewed / Open Access
• [Journal Article] Non-degradable autophagic vacuoles are indispensable for cell competition (2022)
  • Author(s): Akter Eilma、Tasaki Yukihiro、Mori Yusuke、Nakai Kazuki、Hachiya Kazuki、Lin Hancheng、Konno Masamitsu、Kamasaki Tomoko、Tanabe Kenji、Umeda Yumi、Yamano Shotaro、Fujita Yasuyuki、Kon Shunsuke
  • Journal Title: Cell Reports Volume: 40 Issue: 9 Pages: 111292-111292
  • DOI: 10.1016/j.celrep.2022.111292
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Dose-response relationship of pulmonary disorders by inhalation exposure to cross-linked water-soluble acrylic acid polymers in F344 rats (2022)
  • Author(s): Takeda T, Yamano S, Goto Y, Hirai S, Furukawa Y, Kikuchi Y, Misumi K, Suzuki M, Takanobu K, Senoh H, Saito M, Kondo H, Daghlian G, Hong YK, Yoshimatsu Y, et al.
  • Journal Title: Particle Fibre and Toxicology Volume: 19 Issue: 1
  • DOI: 10.1186/s12989-022-00468-9
  • Peer Reviewed / Open Access / Int'l Joint Research