| Title: | Effects of obesity on CC16 and their potential role in overweight/obese asthma |
| Authors: | Goudarzi, Houman Browse this author |
| Kimura, Hirokazu Browse this author |
| Kimura, Hiroki Browse this author |
| Makita, Hironi Browse this author |
| Matsumoto, Munehiro Browse this author |
| Takei, Nozomu Browse this author |
| Shimizu, Kaoruko Browse this author |
| Suzuki, Masaru Browse this author |
| Watanabe, Taku Browse this author |
| Kikuchi, Eiki Browse this author |
| Ohira, Hiroshi Browse this author |
| Tsujino, Ichizo Browse this author |
| Sakakibara-Konishi, Jun Browse this author |
| Shinagawa, Naofumi Browse this author |
| Shijubo, Noriharu Browse this author |
| Sato, Hirokazu Browse this author |
| Shigehara, Katsunori Browse this author |
| Kaga, Kichizo Browse this author |
| Hida, Yasuhiro Browse this author |
| Murakami, Soichi Browse this author |
| Ebihara, Yuma Browse this author |
| Nakamura, Akinobu Browse this author |
| Miyoshi, Hideaki Browse this author |
| Hirano, Satoshi Browse this author |
| Hizawa, Nobuyuki Browse this author |
| Atsumi, Tatsuya Browse this author |
| Huang, Shau-ku Browse this author |
| Ito, Yoichi M. Browse this author |
| Nishimura, Masaharu Browse this author |
| Konno, Satoshi Browse this author →KAKEN DB |
| Keywords: | CC16 |
| Overweight and obesity |
| BMI |
| Asthma |
| Clinical asthma measures |
| Issue Date: | 29-Jun-2022 |
| Publisher: | BioMed Central |
| Journal Title: | Respiratory Research |
| Volume: | 23 |
| Issue: | 1 |
| Start Page: | 174 |
| Publisher DOI: | 10.1186/s12931-022-02038-1 |
| Abstract: | 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. |
| Type: | article |
| URI: | http://hdl.handle.net/2115/86799 |
| Appears in Collections: | 医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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