Molecular mechanism of smoking-related health damage

• Project/Area Number: 15K01712
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Applied health science
• Research Institution: Osaka University
• Principal Investigator: Takihara Keiko 大阪大学, キャンパスライフ健康支援センター, 教授 (70252640)
• Project Period (FY): 2015-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 喫煙 / 生活習慣病 / 慢性炎症 / 老化 / 睡眠 / 健康 / 炎症 / ストレス / 性差 / 酸化ストレス / 動脈硬化

Outline of Final Research Achievements

Smoking is considered as an environmental aging accelerator. In the present study, we focused on the influence of smoking to the serum concentration of anti-aging protein a-klotho and the b-klotho-associated protein, fibroblast growth factor (FGF)-21. Serum levels of FGF-21, a-klotho, and inflammation-related cytokine IL-6 were significantly higher in smokers than in never-smokers in male subjects. However, in female subjects, a-klotho levels were slightly lower in smokers than in never-smokers. Klotho-related molecules showed a differential association and response to smoking between men and women.
We further focused on the serum levels of a-klotho as a possible objective biomarker of stress. Among male subjects, a-klotho was significantly elevated who had poor stress management and unsatisfactory sleep, suggesting that stress management influenced the serum levels of a-klotho.

Academic Significance and Societal Importance of the Research Achievements

喫煙をはじめとしたライフスタイルの変化が、老化・炎症という観点からメタボリックシンドローム発症リスク因子としてどのような意義をもつのかを科学的に明らかにすることにより、生活習慣病予防へとつながるライフスタイルの改善に向けた新たな予防法・生活指導法を確立することが可能となる。また、睡眠やストレスがいかにして生活習慣病発症に関わるのかについて、男女の違いを明らかにすることにより、男女別の予防法や生活指導法を確立することが可能となる。

Research Products

• [Journal Article] An implication of alpha-Klotho as the predictive factor of stress: A cross-sectional study. (2019)
  • Author(s): K. Nakanishi, M. Nishida, M. Taneike, R. Yamamoto, H. Adachi, T. Moriyama, K. Yamauchi-Takihara.
  • Journal Title: J Invest Med Volume: 印刷中
  • Peer Reviewed
• [Journal Article] An implication of Klotho-related molecules in different smoking-related health outcomes between men and women (2018)
  • Author(s): Nakanishi Kaori、Nishida Makoto、Yamamoto Ryohei、Koseki Masahiro、Moriyama Toshiki、Yamauchi-Takihara Keiko
  • Journal Title: Clin Chim Acta Volume: 476 Pages: 44-48
  • DOI: 10.1016/j.cca.2017.11.007
  • Peer Reviewed / Open Access
• [Journal Article] Women among First Authors in Japanese Cardiovascular Journal (2018)
  • Author(s): T. Fujii, T. Matsuyama, J. Takeuchi, M. Hara, T. Kitamura, K. Yamauchi-Takihara.
  • Journal Title: International Heart Journal Volume: 59 Issue: 2 Pages: 372-377
  • DOI: 10.1536/ihj.17-187
  • NAID: 130006589018
  • ISSN: 1349-2365, 1349-3299
  • Peer Reviewed / Open Access
• [Journal Article] Successful treatment of severe combined post- and pre- capillary pulmonary hypertension in a patient with idiopathic restrictive cardiomyopathy. (2018)
  • Author(s): S. Ishihara, H. Kioka, T. Ohtani, Y. Asano, O. Yamaguchi, S. Hikoso, K. Toda, Y. Saito, Y. Sawa, K. Yamauchi-Takihara, Y. Sakata
  • Journal Title: Pulm Circ Volume: 8 Issue: 3 Pages: 1-5
  • DOI: 10.1177/2045894018770131
  • Peer Reviewed / Open Access
• [Journal Article] 受動喫煙の危険性を識る (2018)
  • Author(s): 瀧原圭子
  • Journal Title: Therapuetic Research Volume: 39 Pages: 839-840
• [Journal Article] Interferon Therapy Exacerbated Pulmonary Hypertension in a Patient with Hepatitis C Virus Infection: Pathogenic Interplay among Multiple Risk Factors (2017)
  • Author(s): H. Tsuchiya, H. Kioka, K. Ozu, T. Ohtani, O. Yamaguchi, Y. Yazaki, K. Yamauchi-Takihara, Y. Sakata
  • Journal Title: Internal Medicine Volume: 56 Issue: 9 Pages: 1061-1065
  • DOI: 10.2169/internalmedicine.56.7822
  • NAID: 130005632048
  • ISSN: 0918-2918, 1349-7235
  • Peer Reviewed
• [Journal Article] Association between N-terminal pro-brain natriuretic peptide and adiponectin in healthy Japanese men. (2016)
  • Author(s): Nakanishi K, Nishida M, Yamamoto R, Koseki M, Moriyama T, Yamauchi-Takihara K.
  • Journal Title: Clin Chim Acta Volume: 460 Pages: 138-141
  • DOI: 10.1016/j.cca.2016.06.029
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Molecular Characterization of Striated Muscle-specific Gab1Isoform as aCritical Signal Transducer for Neuregulin-1/ErbB Signaling in Cardiomyocytes. (2016)
  • Author(s): Yasui T,Masaki T,Arita Y,Ishibashi T,Inagaki T,Okazawa M,Oka T,Shioyama W,Yamauchi-Takihara K,Komuro I,Sakata Y,Nakaoka Y.
  • Journal Title: PlosOne Volume: 11 Issue: 11 Pages: e0166710-e0166710
  • DOI: 10.1371/journal.pone.0166710
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Is It Possible to Predict the Onset of “Heart Failure” in Hypertrophic Cardiomyopathy? (2016)
  • Author(s): Yamauchi-Takihara K.
  • Journal Title: Circulation Journal Volume: 80 Issue: 1 Pages: 67-68
  • DOI: 10.1253/circj.CJ-15-1234
  • NAID: 130005117017
  • ISSN: 1346-9843, 1347-4820
  • Peer Reviewed / Open Access
• [Journal Article] 第80回日本循環器学会学術集会レポート 循環器疾患における性差医療 (2016)
  • Author(s): 瀧原圭子
  • Journal Title: 医学のあゆみ Volume: 257 Pages: 1196-1198
• [Journal Article] 新入生健診におけるメンタルヘルスチェック尺度の年次比較－3年間の性別、学部別分析－ (2016)
  • Author(s): 足立由美、水田一郎、工藤喬、足立浩祥、谷向仁、壁下康信、石金直美、竹中菜苗、守山敏樹、瀧原圭子.
  • Journal Title: CAMPUS HEALTH Volume: 52 Pages: 149-154
  • NAID: 40022282052
  • Peer Reviewed
• [Journal Article] 喫煙と老化 (2016)
  • Author(s): 西田誠、中西香織、瀧原圭子
  • Journal Title: 循環器専門医 Volume: 24 Pages: 295-299
• [Journal Article] 喫煙と老化 (2016)
  • Author(s): 西田 誠、中西 香織、瀧原圭子
  • Journal Title: 循環器専門医 Volume: 24 Pages: 0-0
• [Journal Article] Klotho-related molecules upregulated by smoking habit in apparently healthy men: A cross sectional study. (2015)
  • Author(s): K. Nakanishi, M. Nishida, M. Harada, T. Ohama, N. Kawada, M. Murakami, T. Moriyama, K. Yamauchi-Takihara.
  • Journal Title: Scientific Reports Volume: 5 Issue: 1 Pages: 14230-14230
  • DOI: 10.1038/srep14230
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Interleukin-6/interleukin-21 signaling axis is critical in the pathogenesis of pulmonary arterial hypertension (2015)
  • Author(s): Hashimoto-Kataoka T, Hosen N, Sonobe T, Arita Y, Yasui T, Masaki T, Minami M, Inagaki T, Miyagawa S, Sawa Y, Murakami M, Kumanogoh A, Yamauchi-Takihara K, Okumura M, Kishimoto T, Komuro I, Shirai M, Sakata Y, and Nakaoka Y
  • Journal Title: Proceedings of the National Academy of Sciences of the United States of America Volume: Early Edition Issue: 20 Pages: 1-10
  • DOI: 10.1073/pnas.1424774112
  • Peer Reviewed / Open Access
• [Journal Article] Cytokine storm after cessation of tocilizumab in a patient with refractory Takayasu arteritis. (2015)
  • Author(s): Arita Y, Nakaoka Y, Otsuki M, Higuchi K, Hashimoto-Kataoka T, Yasui T, Masaki T, Ohtani T, Kishimoto T, Yamauchi-Takihara K, Komuro I, Sakata Y.
  • Journal Title: International Journal of Cardiology Volume: 187 Pages: 319-321
  • DOI: 10.1016/j.ijcard.2015.03.399
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Temporal expression of growth factors triggered by epiregulin regulates inflammation development. (2015)
  • Author(s): Harada, M., Kamimura, D., Arima, Y., Kohsaka, H., Nakatsuji, Y., Nishida, M., Atsumi, T., Meng, J., Bando, H., Singh, R., Sabharwal, L., Jiang, J. J., Kumai, N., Miyasaka, N., Sakoda, S., Yamauchi-Takihara, K., Ogura, H., Hirano, T. & Murakami, M.
  • Journal Title: J Immunol Volume: 194 Issue: 3 Pages: 1039-1046
  • DOI: 10.4049/jimmunol.1400562
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Sex-differential Associations of Klotho-related Molecules with Smoking-related Health Risks (2019)
  • Author(s): M. Nishida, K. Nakanishi, T. Moriyama, K. Yamauchi-Takihara
  • Organizer: 第83回日本循環器学会学術集会
• [Presentation] 飲酒による高血圧発症リスクは性別とBMIにより異なる (2018)
  • Author(s): 鶴飼朱美、山本陵平、明石美智子、梅野有希、川村淳子、熊谷一代 村井教子、姫ヶ迫由美、中西香織、種池学、西田誠、瀧原圭子、 守山敏樹
  • Organizer: 第56回全国大学保健管理研究集会
• [Presentation] 精神障がい学生に対する合理的配慮の検討に関する取り組み (2018)
  • Author(s): 諏訪 絵里子，金山 大祐，足立 浩祥，工藤 喬，稲月 聡子，水田 一郎， 瀧原 圭子，守山 敏樹
  • Organizer: 第56回全国大学保健管理研究集会
• [Presentation] 喫煙による健康障害における性差 (2018)
  • Author(s): 瀧原圭子
  • Organizer: 第50回日本動脈硬化学会学術集会
  • Invited
• [Presentation] Sex Differences of Klotho-related Molecules in Smoking-related Health Damage. (2018)
  • Author(s): K. Yamauchi-Takihara
  • Organizer: 第82回日本循環器学会学術集会 シンポジウム
• [Presentation] Serum soluble a-klotho levels were elevated in male smokers but not in female smokers. (2018)
  • Author(s): K. Nakanishi, M. Nishida, K. Yamauchi-Takihara.
  • Organizer: 第82回日本循環器学会学術集会
• [Presentation] Association of Cardiovascular Risk Factors and Life Style with the Changes of Waist Circumference -10 Years Follow-up- (2017)
  • Author(s): M. Nishida、K. Nakanishi、M. Koseki、K. Takihara
  • Organizer: 第81 回日本循環器学会学術集会
  • Place of Presentation: 金沢
  • Year and Date: 2017-03-17
• [Presentation] Sex Differences of Klotho-related Molecules in Smoking-related Health Damage. (2017)
  • Author(s): K. Nakanishi, M. Nishida, R. Yamamoto, M. Koseki, T. Moriyama, K. Yamauchi-Takihara
  • Organizer: The 8th Congress of the International Society for Gender Medicine
  • Int'l Joint Research
• [Presentation] The molecular link between atherosclerosis and non-alcoholic steatohepatitis. (2017)
  • Author(s): M. Koseki, K. Yamauchi-Takihara, Y. Sakata.
  • Organizer: 第34回国際心臓研究学会日本部会
• [Presentation] ストレスチェック開始後一年間の取り組みのまとめと現状報告 (2017)
  • Author(s): 川村淳子、足立浩祥、明石美智子、熊谷一代、村井 教子、姫ヶ迫由美、金山大祐、西田 誠、山本陵平、小関正博、中西香織、岡 久仁洋、瀧原圭子、工藤 喬、守山敏樹
  • Organizer: 第55回全国大学保健管理研究集会
• [Presentation] The association between N-terminal pro-brain natriuretic peptide and adiponectin in healthy subjects (2016)
  • Author(s): K. Nakanishi, M. Nishida, M. Koseki, K. Yamauchi-Takihara
  • Organizer: 第33回国際心臓研究学会(ISHR) 日本部会
  • Place of Presentation: 東京
  • Year and Date: 2016-12-16
• [Presentation] 喫煙による老化促進におけるクロトー関連分子の関与について (2016)
  • Author(s): 中西香織、西田誠、瀧原圭子
  • Organizer: 第20回日本適応医学会学術集会
  • Place of Presentation: 東京
  • Year and Date: 2016-12-16
• [Presentation] 10年間のBMI・腹囲増減に伴う健康障害と生活習慣の関連 (2016)
  • Author(s): 梅野有希，西田 誠，川村淳子，村井教子，熊谷一代，中西香織，小関正博，山本陵平，守山敏樹，瀧原圭子
  • Organizer: 第54回全国大学保健管理研究集会
  • Place of Presentation: 大阪
  • Year and Date: 2016-10-06
• [Presentation] 夜間業務頻度と蛋白尿 (2016)
  • Author(s): 村井教子、山本陵平、川村淳子、明石美智子、梅野有希、 熊谷一代、中西香織、壁下康信、小関正博、金山大祐、 足立浩祥、西田誠、水田一郎、工藤喬、守山敏樹、 瀧原圭子
  • Organizer: 第54回全国大学保健管理研究集会
  • Place of Presentation: 大阪
  • Year and Date: 2016-10-06
• [Presentation] Smoking upregulates the serum levels of Klotho-related molecules (2016)
  • Author(s): Nakanishi K, Nishida M, Murakami M, Moriyama T, Yamauchi-Takihara K
  • Organizer: 米国胸部学会議（ATS 2016 International Conference）
  • Place of Presentation: サンフランシスコ
  • Year and Date: 2016-05-13
  • Int'l Joint Research
• [Presentation] Smoking Affects the Associations of Klotho-related Molecules, FGF-21 and Klotho, with Metabolic Disorders and Anti-inflammatory Network. (2016)
  • Author(s): Makoto Nishida, Kaori Nakanishi, Masahiro Koseki, Keiko Takihara
  • Organizer: 第80回日本循環器学会学術集会
  • Place of Presentation: 仙台
  • Year and Date: 2016-03-18
• [Presentation] 大学内全面禁煙に向けての取り組みと、 その効果について (2015)
  • Author(s): 石山奈緒美、梅野有希、川村淳子、明石美智子、中西香織、熊谷一代、村井教子 姫ヶ迫由美、小関正博、山本陵平、西田 誠、守山敏樹、瀧原圭子
  • Organizer: 第53回全国大学保健管理研究集会
  • Place of Presentation: 盛岡
  • Year and Date: 2015-09-09
• [Presentation] 喫煙を科学する (2015)
  • Author(s): 瀧原圭子
  • Organizer: 第4回禁煙治療研究会
  • Place of Presentation: 京都
  • Year and Date: 2015-05-24
• [Presentation] 喫煙による老化促進について (2015)
  • Author(s): 中西香織
  • Organizer: 第55回日本呼吸器学会学術集会
  • Place of Presentation: 東京
  • Year and Date: 2015-04-17