環境中化学物質による気管支喘息症の中心的役割としてのエクソソームとそのmiRNA

2022 Fiscal Year Annual Research Report

• Project/Area Number: 19H03882
• Research Institution: Kanazawa University
• Principal Investigator: 中村 裕之 金沢大学, 医学系, 教授 (30231476)
• Co-Investigator(Kenkyū-buntansha): 辻口 博聖 金沢大学, 医学系, 特任助教 (00723090) ; 神林 康弘 岡山理科大学, 獣医学部, 教授 (20345630) ; 早川 和一 金沢大学, 環日本海域環境研究センター, 連携研究員 (40115267) ; 尾長谷 靖 長崎大学, 医歯薬学総合研究科(医学系), 准教授 (40399762) ; 華山 力成 金沢大学, ナノ生命科学研究所, 教授 (40403191) ; 中島 美紀 金沢大学, ナノ生命科学研究所, 教授 (70266162) ; 原 章規 金沢大学, 医学系, 准教授 (70507045)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: 気管支喘息症 / 多環芳香族炭化水素類 / 大気汚染 / エクソソーム / miRNA

Outline of Annual Research Achievements

アレルギーと炎症をクロストークする病態として化学物質による気管支喘息発症において好酸球から放出されるエクソソームとそのmiRNAの役割を解明するために、気管支喘息、アトピー性咳嗽あるいは咳喘息を有する患者40人を対象に、血液中から好酸球を分離し、エクソソームを抽出し、その数をナノ粒子カウンターでカウントした。さらにエクソームからtotal RNAを抽出し、RNA量と大きさを測定し、好酸球におけるエクソソームmiRNAの発現プロファイルを解析した。また喫煙歴の有無、教育歴（10年間以上か未満か）などの情報を収集し、同時に周辺領域の大気中の二酸化窒素(NO2)および多環芳香族炭化水素類（PAH）やPM2.5などの微小粒子状物質を測定した。またアレルギー日記にて毎日の咳、痰、喘鳴などに関する症状調査を行った。miRNAに対する気管支喘息の有無とPAH濃度およびPM2.5濃度の高低による二元配置共分散分析（共変量として年齢、BMIおよび喫煙歴）の結果、PAH濃度およびPM2.5濃度のいずれにおいてもmiR-146などの発現プロファイルに対する交互作用がみられることが確認された。すなわち、PAH濃度およびPM2.5に対する曝露が大きい群の気管支喘息を有する群のmiR-146量などは気管支喘息症を有さない群のそれに比べて高いことが認められた。PAH濃度およびPM2.5濃度の低い群では、この関係が成り立たなかった。ベンゾ[a]ピレン （BaP）において群分けした場合も同様の結果が得られた。NO2に対しては交互作用が認められなかった。この結果は、BaPなどのPAHが気管支喘息を発症する病態として、好酸球からエクソソームとmiRNA、特にmiR-146などの役割が大きいことを示唆する結果であった。したがって大気中のBaPなどのPAHのモニタリングと同時に、好酸球からエクソソームのmiR-146などのプロファイルを測定することによって大気中の化学物質による気管支喘息症発症を予防できると考えられた。

Research Progress Status

令和4年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

令和4年度が最終年度であるため、記入しない。

Research Products

• [Journal Article] Acceptability of transdermal antipsychotic patches by patients who refuse oral medication and their effectiveness in preventing recurrence of delirium: a retrospective observational study (2023)
  • Author(s): Kotaro Hatta, Chie Usui, Hiroyuki Nakamura
  • Journal Title: International Clinical Psychopharmacology Publish Ahead of Print Volume: 38(1) Pages: 23-27
  • DOI: 10.1097/yic.0000000000000428
  • Peer Reviewed / Open Access
• [Journal Article] Genetic factors associated with serum amylase in a Japanese population: combined analysis of copy-number and single-nucleotide variants (2023)
  • Author(s): Zannatun Nayema, Takehiro Sato, Takayuki Kannon, Hiromasa Tsujiguchi, Kazuyoshi Hosomichi, Hiroyuki Nakamura, Atsushi Tajima
  • Journal Title: Journal of Human Genetics Volume: 68 Pages: 313-319
  • DOI: 10.1038/s10038-022-01111-3
  • Peer Reviewed / Open Access
• [Journal Article] Relationships among Depressive Symptoms, Body Weight, and Chronic Pain: A Cross-Sectional Analysis of the Shika Study (2023)
  • Author(s): Shinobu Fukushima, Hiroyuki Nakamura（20人中20番目）
  • Journal Title: Behavioral Sciences Volume: 13(2) Pages: 86-86
  • DOI: 10.3390/bs13020086
  • Peer Reviewed / Open Access
• [Journal Article] Association between Bone Mineral Density and Oral Frailty on Renal Function: Findings from the Shika Study (2023)
  • Author(s): Shingo Nakai, Fumihiko Suzuki, Shigefumi Okamoto, Hiromasa Tsujiguchi, Akinori Hara, Yukari Shimizu, Koichiro Hayashi, Keita Suzuki, Tomoko Kasahara, Masaharu Nakamura, Chie Takazawa, Takayuki Kannon, Atsushi Tajima, Hirohito Tsuboi, Noriyoshi Ogino, Tadashi Konoshita, Toshinari Takamura, Hiroyuki Nakamura
  • Journal Title: Healthcare Volume: 11(3) Pages: 314-314
  • DOI: 10.3390/healthcare11030314
  • Peer Reviewed / Open Access
• [Journal Article] Higher Intake of Vegetable Protein and Lower Intake of Animal Fats Reduce the Incidence of Diabetes in Non-Drinking Males: A Prospective Epidemiological Analysis of the Shika Study (2023)
  • Author(s): Aya Ogawa, Hiromasa Tsujiguchi, Masaharu Nakamura, Koichi Hayashi, Akinori Hara, Keita Suzuki, Sakae Miyagi, Takayuki Kannon, Chie Takazawa, Jiaye Zhao, Yasuhiro Kambayashi, Yukari Shimizu, Aki Shibata, Tadashi Konoshita, Fumihiko Suzuki, Hirohito Tsuboi, Atsushi Tajima, Hiroyuki Nakamura
  • Journal Title: Nutrients Volume: 15(4) Pages: 1040-1040
  • DOI: 10.3390/nu15041040
  • Peer Reviewed / Open Access
• [Journal Article] Identification of risk factors for elevated serum IgG4 levels in subjects in a large-scale health checkup cohort study (2023)
  • Author(s): Yoshika Tsuji , Tomohiro Koga , Fumiaki Nonaka , Kenichi Nobusue , Shin-Ya Kawashiri , Hirotomo Yamanashi , Takahiro Maeda , Kazuhiko Arima , Kiyoshi Aoyagi , Meiko Takahashi , Shuji Kawaguchi , Fumihiko Matsuda , Hiroshi Fujii , Mitsuhiro Kawano , Hiroyuki Nakamura , Atsushi Kawakami , Mami Tamai
  • Journal Title: Front Immunol Volume: 14 Pages: 1124417
  • DOI: 10.3389/fimmu.2023.1124417
  • Peer Reviewed / Open Access
• [Journal Article] Sex differences in risk factors for end-stage kidney disease and death in type 2 diabetes: A retrospective cohort study (2023)
  • Author(s): Megumi Oshima, Hiroyuki Nakamura（23人中22番目）
  • Journal Title: J Diabetes Volume: 15(3) Pages: 246-254
  • DOI: 10.1111/1753-0407.13367
  • Peer Reviewed / Open Access
• [Journal Article] Acceptability of transdermal antipsychotic patches by patients who refuse oral medication and their effectiveness in preventing recurrence of delirium: a retrospective observational study (2023)
  • Author(s): Kotaro Hatta , Chie Usui , Hiroyuki Nakamura
  • Journal Title: Int Clin Psychopharmacol Volume: 38(1) Pages: 23-27
  • DOI: 10.1097/YIC.0000000000000428
  • Peer Reviewed / Open Access
• [Journal Article] Association between vitamin intake and chronic kidney disease according to a variant located upstream of the PTGS1 gene: A cross-sectional analysis of Shika study (2022)
  • Author(s): Kim-Oanh Pham, Hiroyuki Nakamura（21人中21番目）
  • Journal Title: Nutrients Volume: 14(10) Pages: 2082
  • DOI: 10.3390/nu14102082
  • Peer Reviewed / Open Access
• [Journal Article] Association between serum 25-hydroxyvitamin D concentrations, CDX2 polymorphism in promoter region of vitamin D receptor gene, and chronic pain in rural Japanese residents (2022)
  • Author(s): Keita Suzuki, Hiroyuki Nakamura（19人中19番目）
  • Journal Title: Journal of Pain Research Volume: 15 Pages: 1475-1485
  • DOI: 10.2147/JPR.S356630
  • Peer Reviewed / Open Access
• [Journal Article] Association between dietary fat intake and hyperuricemia in men with chronic kidney disease (2022)
  • Author(s): Fumika Oku, Akinori Hara, Hiromasa Tsujiguchi, Keita Suzuki, Kim-Oanh Pham, Fumihiko Suzuki, Sakae Miyagi, Masaharu Nakamura, Chie Takazawa, Kuniko Sato, Toru Yanagisawa, Takayuki Kannon, Atsushi Tajima, Hiroyuki Nakamura
  • Journal Title: Nutrients Volume: 14(13) Pages: 2637-2637
  • DOI: 10.3390/nu14132637
  • Peer Reviewed / Open Access
• [Journal Article] Relationship between fatty acid intake and chronic neck/shoulder/upper limb pain without elevated CRP in a Japanese population: A cross-sectional analysis of the Shika study (2022)
  • Author(s): Atsushi Asai, Hiroyuki Nakamura（21人中21番目）
  • Journal Title: Journal of Nutritional Science Volume: 11 Pages: -
  • DOI: 10.1017/jns.2022.37
  • Peer Reviewed / Open Access
• [Journal Article] Different Transport Behaviors between Asian Dust and Polycyclic Aromatic Hydrocarbons in Urban Areas: Monitoring in Fukuoka and Kanazawa, Japan (2022)
  • Author(s): Kim-Oanh Pham, Akinori Hara, Jiaye Zhao, Keita Suzuki, Atsushi Matsuki, Yayoi Inomata, Hiroshi Matsuzaki, Hiroshi Odajima, Kazuichi Hayakawa, Hiroyuki Nakamura
  • Journal Title: Applied Sciences Volume: 12(11) Pages: 5404-5404
  • DOI: 10.3390/app12115404
  • Peer Reviewed / Open Access
• [Journal Article] Analysis of Chemical Components of Fine Particulate Matter Observed at Fukuoka, Japan, in Spring 2020 and Their Transport Paths (2022)
  • Author(s): Ayako Yoshino, Akinori Takami, Atsushi Shimizu, Kei Sato, Kazuichi Hayakawa, Ning Tang, Kim-Oanh Pham, Akinori Hara, Hiroyuki Nakamura, Hiroshi Odajima
  • Journal Title: Applied Sciences Volume: 12(22) Pages: 11400-11400
  • DOI: 10.3390/app122211400
  • Peer Reviewed / Open Access
• [Journal Article] Efficacy of Mask Wearing in Preventing the Deleterious Health Effects of the Ionic Components of PM25-Possibility Seen in Allergic Patients (2022)
  • Author(s): Hiroshi Odajima, Hiroshi Matsuzaki, Yuko Akamine, Kaoru Kojima, Yoko Murakami, Ayako Yoshino, Akinori Takami, Kazuichi Hayakawa, Akinori Hara, Hiroyuki Nakamura
  • Journal Title: Applied Sciences Volume: 12(21) Pages: 11185-11185
  • DOI: 10.3390/app122111185
  • Peer Reviewed / Open Access
• [Journal Article] Impact of gut microbiome on dyslipidemia in japanese adults: Assessment of the Shika-machi super preventive health examination results for causal inference (2022)
  • Author(s): Yuna Miyajima, Shigehiro Karashima, Kazuhiro Ogai, Kouki Taniguchi, Kohei Ogura, Masaki Kawakami, Hidetaka Nambo, Mitsuhiro Kometani, Daisuke Aono, Masashi Demura, Takashi Yoneda, Hiromasa Tsujiguchi, Akinori Hara, Hiroyuki Nakamura, Shigefumi Okamoto
  • Journal Title: Frontiers in Cellular and Infection Microbiology Volume: 12(3) Pages: 145-153
  • DOI: 10.3389/fcimb.2022.908997
  • Peer Reviewed / Open Access
• [Journal Article] Relationship between vitamin intake and resilience based on sex in middle-aged and older Japanese adults: Results of the Shika study (2022)
  • Author(s): Kuniko Sato, Fumihiko Suzuki, Hiromasa Tsujiguchi, Akinori Hara, Takayuki Kannon, Sakae Miyagi, Keita Suzuki, Masaharu Nakamura, Chie Takazawa, Aki Shibata, Hirohito Tsuboi, Yukari Shimizu, Thao Thi Thu Nguyen, Tadashi Konoshita, Yasuki Ono, Koichi Hayashi, Atsushi Tajima, Hiroyuki Nakamura
  • Journal Title: Nutrients Volume: 14(23) Pages: 5042-5042
  • DOI: 10.3390/nu14235042
  • Peer Reviewed / Open Access
• [Journal Article] Bone strength of the calcaneus Is associated with dietary calcium intake in older Japanese men, but not women (2022)
  • Author(s): Keita Suzuki, Hiromasa Tsujiguchi, Akinori Hara, Sakae Miyagi, Thao Thi Thu Nguyen, Yasuhiro Kambayashi, Yukari Shimizu, Fumihiko Suzuki, Chie Takazawa, Masaharu Nakamura, Hirohito Tsuboi, Takayuki Kannon, Atsushi Tajima, Hiroyuki Nakamura
  • Journal Title: Nutrients Volume: 14(24) Pages: 5225-5225
  • DOI: 10.3390/nu14245225
  • Peer Reviewed / Open Access
• [Journal Article] Cystatin C-based eGFR predicts cardiovascular disease in patients with overweight/obesity and hyperglycemia (2022)
  • Author(s): Keita Suzuki, Hiromasa Tsujiguchi, Akinori Hara, Hiroyuki Nakamura, Kazuhiko Kotani, Mitsuhiko Noda, Hajime Yamakage, Noriko Satoh-Asahara, Toshinari Takamura
  • Journal Title: Obesity Science and Practice Volume: 9(1) Pages: 4-14
  • DOI: 10.1002/osp4.630
  • Peer Reviewed / Open Access
• [Journal Article] Elevated ratio of serum anandamide to arachidonic acid intake in community-dwelling women with high depressive symptoms (2022)
  • Author(s): Hirohito Tsuboi, Masahiro Matsunaga, Hiromasa Tsujiguchi, Takayuki Kannon, Kazuyoshi Hosomichi, Takehiro Sato, Atsushi Tajima, Naoko Yoshida, Akinori Hara, Hiroyuki Nakamura
  • Journal Title: Neuro endocrinology letters Volume: 43(3) Pages: 145-153
  • Peer Reviewed / Open Access
• [Journal Article] Association between cough and ambient polycyclic aromatic hydrocarbons in patients with chronic cough: an observational study in two regions of Japan (2022)
  • Author(s): Akinori Hara, Hiroshi Odajima, Hiroshi Matsuzaki, Masaki Fujimura, Tomoko Toma, Taizo Wada, Noriyuki Ohkura, JiaYe Zhao, Kim-Oanh Pham, Keita Suzuki, Hiromasa Tsujiguchi, Akinori Takami, Kazuichi Hayakawa, Hiroyuki Nakamura
  • Journal Title: Applied Sciences Volume: 12(24) Pages: 12505
  • DOI: 10.3390/app122412505
  • Peer Reviewed / Open Access
• [Journal Article] Prospective relationship between autistic traits and nutrient intakes among Japanese children: Results of the Shika study (2022)
  • Author(s): Hiromasa Tsujiguchi, Akinori Hara, Sakae Miyagi, Kim Oanh Pham, Keita Suzuki, Thao Thi Thu Nguyen, Yasuki Ono, Yasuhiro Kambayashi, Yukari Shimizu, Haruki Nakamura, Fumihiko Suzuki, Aki Shibata, Koichi Hayashi, Hirohito Tsuboi, Hiroyuki Nakamura
  • Journal Title: Autism Volume: 27(2) Pages: 389-401
  • DOI: 10.1177/136236132210974
  • Peer Reviewed / Open Access
• [Journal Article] The Role of Polygenic Susceptibility on Air Pollution-Associated Asthma between German and Japanese Elderly Women (2022)
  • Author(s): Sara Kress, Akinori Hara, Claudia Wigmann, Takehiro Sato, Keita Suzuki, Kim-Oanh Pham, Qi Zhao, Ashtyn Areal, Atsushi Tajima, Holger Schwender, Hiroyuki Nakamura, Tamara Schikowski
  • Journal Title: International Journal of Environmental Research and Public Health Volume: 19(16) Pages: 9869-9869
  • DOI: 10.3390/ijerph19169869
  • Peer Reviewed / Open Access
• [Journal Article] Relationship between Social Capital and Depressive Symptoms: Differences According to Resilience and Gender in the Shika Study (2022)
  • Author(s): Kuniko Sato, Hiromasa Tsujiguchi, Fumihiko Suzuki, Akinori Hara, Takayuki Kannon, Go Muto, Daisuke Hori, Sakae Miyagi, Keita Suzuki, Masaharu Nakamura, Chie Takazawa, Tomoko Kasahara, Hirohito Tsuboi, Mie Matsui, Atsushi Tajima, Hiroyuki Nakamura
  • Journal Title: Journal of Affective Disorders Reports Volume: 10 Pages: 100421-100421
  • DOI: 10.1016/j.jadr.2022.100421
  • Peer Reviewed / Open Access
• [Journal Article] Comparison of Tofogliflozin and Glimepiride Effects on Nonalcoholic Fatty Liver Disease in Participants With Type 2 Diabetes: A Randomized, 48-Week, Open-Label, Active-Controlled Trial (2022)
  • Author(s): Yumie Takeshita, Masao Honda, Kenichi Harada, Yuki Kita, Noboru Takata, Hiromasa Tsujiguchi, Takeo Tanaka, Hisanori Goto, Yujiro Nakano, Noriho Iida, Kuniaki Arai, Tatsuya Yamashita, Eishiro Mizukoshi, Hiroyuki Nakamura, Shuichi Kaneko, Toshinari Takamura
  • Journal Title: Diabetes care Volume: 45(9) Pages: 2064-2075
  • DOI: 10.2337/dc21-2049
  • Peer Reviewed / Open Access
• [Journal Article] Seasonal Variability and Risk Assessment of Atmospheric Polycyclic Aromatic Hydrocarbons and Hydroxylated Polycyclic Aromatic Hydrocarbons in Kanazawa, Japan (2022)
  • Author(s): Masato Honda, Kazuichi Hayakawa, Lulu Zhang, Ning Tang, Hiroyuki Nakamura
  • Journal Title: Applied Sciences Volume: 12(19) Pages: 9469-9469
  • DOI: 10.3390/app12199469
  • Peer Reviewed / Open Access
• [Journal Article] The Ionic Component of PM25 May Be Associated with Respiratory Symptoms and Peak Expiratory Flow Rate (2022)
  • Author(s): Hiroshi Odajima, Hiroshi Matsuzaki, Yuko Akamine, Kaoru Kojima, Yoko Murakami, Ayako Yoshino, Akinori Takami, Kazuichi Hayakawa, Akinori Hara, Hiroyuki Nakamura
  • Journal Title: Applied Sciences Volume: 12(19) Pages: 10082-10082
  • DOI: 10.3390/app121910082
  • Peer Reviewed / Open Access
• [Journal Article] Hypertension and Low Body Weight Are Associated with Depressive Symptoms Only in Females: Findings from the Shika Study (2022)
  • Author(s): Toru Yanagisawa, Fumihiko Suzuki, Hiromasa Tsujiguchi, Akinori Hara, Sakae Miyagi, Takayuki Kannon, Keita Suzuki, Yukari Shimizu, Thao Thi Thu Nguyen, Fumika Oku, Kuniko Sato, Masaharu Nakamura, Koichiro Hayashi, Aki Shibata, Tadashi Konoshita, Yasuhiro Kambayashi, Hirohito Tsuboi, Atsushi Tajima, Hiroyuki Nakamura
  • Journal Title: Behavioral Sciences Volume: 12(11) Pages: 413-413
  • DOI: 10.3390/bs12110413
  • Peer Reviewed / Open Access
• [Journal Article] Neutralizing-antibody response to SARS-CoV-2 for 12 months after the COVID-19 workplace outbreaks in Japan (2022)
  • Author(s): Azumi Ishizaki, Xiuqiong Bi, Quynh Thi Nguyen, Tomomi Maeno, Akinori Hara, Hiroyuki Nakamura, Sanae Kuramoto, Koichi Nishi, Hiroyasu Ooe, Hiroshi Ichimura
  • Journal Title: PLOS ONE Volume: 17(8) Pages: -
  • DOI: 10.1371/journal.pone.0273712
  • Peer Reviewed / Open Access
• [Journal Article] Longitudinal Study on the Association between Ambient Polycyclic Aromatic Hydrocarbons and Nasal Symptoms in Adult Japanese (2022)
  • Author(s): Jiaye Zhao, Akinori Hara, Kazuichi Hayakawa, Kim-Oanh Pham, Keita Suzuki, Hiromasa Tsujiguchi, Hiroshi Matsuzaki, Hiroshi Odajima, Akinori Takami, Hiroyuki Nakamura
  • Journal Title: Applied Sciences Volume: 12(24) Pages: 12544-12544
  • DOI: 10.3390/app122412544
  • Peer Reviewed / Open Access
• [Journal Article] Effects of Melissa officinalis Extract Containing Rosmarinic Acid on Cognition in Older Adults Without Dementia: A Randomized Controlled Trial (2022)
  • Author(s): Moeko Noguchi-Shinohara, Tsuyoshi Hamaguchi, Kenji Sakai, Junji Komatsu, Kazuo Iwasa, Mai Horimoto, Hiroyuki Nakamura, Masahito Yamada, Kenjiro Ono
  • Journal Title: Journal of Alzheimer's disease Volume: 91(2) Pages: 805-814
  • DOI: 10.3233/JAD-220953
  • Peer Reviewed / Open Access
• [Journal Article] Selenoprotein P-mediated reductive stress impairs cold-induced thermogenesis in brown fat (2022)
  • Author(s): Swe Mar Oo , Hein Ko Oo , Hiroaki Takayama , Kiyo-Aki Ishii , Yumie Takeshita , Hisanori Goto , Yujiro Nakano , Susumu Kohno , Chiaki Takahashi , Hiroyuki Nakamura , Yoshiro Saito , Mami Matsushita , Yuko Okamatsu-Ogura , Masayuki Saito , Toshinari Takamura
  • Journal Title: Cell Rep Volume: 38(13) Pages: 110566
  • DOI: 10.1016/j.celrep.2022.110566
  • Peer Reviewed / Open Access
• [Journal Article] Diabetes Mellitus, Elevated Hemoglobin A1c, and Glycated Albumin Are Associated with the Presence of All-Cause Dementia and Alzheimer's Disease: The JPSC-AD Study (2022)
  • Author(s): Moeko Noguchi-Shinohara , Sohshi Yuki-Nozaki, Chiemi Abe , Ayaka Mori, Mai Horimoto, Masami Yokogawa, Natsuko Ishida, Yukio Suga, Junko Ishizaki, Mai Ishimiya, Hiroyuki Nakamura , Kiyonobu Komai, Hiroyuki Nakamura, Mao Shibata, Tomoyuki Ohara, Jun Hata, Toshiharu Ninomiya, Masahito Yamada
  • Journal Title: J Alzheimers Dis Volume: 85(1) Pages: 235-247
  • DOI: 10.3233/JAD-215153
  • Peer Reviewed / Open Access
• [Presentation] The role of polygenic susceptibility on air pollution-associated asthma between Caucasian and Asian elderly women (2022)
  • Author(s): Sara Kress, Akinori Hara, Claudia Wigmann, Keita Suzuki, Qi Zhao, Atsushi Tajima, Hiroyuki Nakamura, Tamara Schikowski
  • Organizer: 34th Annual Conferenceof the International Societyfor Environmental Epidemiology
  • Int'l Joint Research