國家衛生研究院 NHRI:Item 3990099045/14435
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    题名: Effects of obesity on CC16 and their potential role in overweight/obese asthma
    作者: Goudarzi, H;Kimura, H;Kimura, H;Makita, H;Matsumoto, M;Takei, N;Shimizu, K;Suzuki, M;Watanabe, T;Kikuchi, E;Ohira, H;Tsujino, I;Sakakibara-Konishi, J;Shinagawa, N;Shijubo, N;Sato, H;Shigehara, K;Kaga, K;Hida, Y;Murakami, S;Ebihara, Y;Nakamura, A;Miyoshi, H;Hirano, S;Hizawa, N;Atsumi, T;Huang, SK;Ito, YM;Nishimura, M;Konno, S
    贡献者: National Institute of Environmental Health Sciences
    摘要: Introduction Club cell secretory protein-16 (CC16) is a major anti-inflammatory protein expressed in the airway; however, the potential role of CC16 on overweight/obese asthma has not been assessed. In this study, we examined whether obesity reduces airway/circulatory CC16 levels using experimental and epidemiological studies. Then, we explored the mediatory role of CC16 in the relationship of overweight/obesity with clinical asthma measures. Methods Circulating CC16 levels were assessed by ELISA in three independent human populations, including two groups of healthy and general populations and asthma patients. The percentage of cells expressing club markers in obese vs. non-obese mice and human airways was determined by immunohistochemistry. A causal mediation analysis was conducted to determine whether circulatory CC16 acted as a mediator between overweight/obesity and clinical asthma measures. Results BMI was significantly and monotonously associated with reduced circulating CC16 levels in all populations. The percentage of CC16-expressing cells was reduced in the small airways of both mice and humans with obesity. Finally, mediation analysis revealed significant contributions of circulatory CC16 in the association between BMI and clinical asthma measures; 21.8% of its total effect in BMI's association with airway hyperresponsiveness of healthy subjects (p = 0.09), 26.4% with asthma severity (p = 0.030), and 23% with the required dose of inhaled corticosteroid (p = 0.042). In logistic regression analysis, 1-SD decrease in serum CC16 levels of asthma patients was associated with 87% increased odds for high dose ICS requirement (p < 0.001). Conclusions We demonstrate that airway/circulating CC16, which is inversely associated with BMI, may mediate development and severity in overweight/obese asthma.
    日期: 2022-06-29
    關聯: Respiratory Research. 2022 Jun 29;23:Article number 174.
    Link to: http://dx.doi.org/10.1186/s12931-022-02038-1
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1465-993X&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000818802500001
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85133141351
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