Physical inactivity is associated with decreased growth differentiation factor 11 in chronic obstructive pulmonary disease

Abstract

Background

Growth differentiation factor 11 (GDF11) is reported to possess anti-aging and rejuvenating effects, including muscle regeneration and to be highly expressed in skeletal muscle. Recently, we demonstrated that the levels of plasma GDF11 were decreased in COPD. However, the effect of decreased circulating GDF11 in the pathophysiology of COPD remains unknown. The aim of this study is to investigate the association between the plasma GDF11 levels and various clinical parameters in patients with COPD.

Patients and methods

Eighteen ex-smokers as control subjects and 70 COPD patients participated in the current study. We measured the levels of plasma GDF11 using immunoblotting, lung function, physical activity using a triaxial accelerometer, quadriceps strength, exercise capacity, and systemic inflammatory markers. We investigated the association between the levels of plasma GDF11 and these clinical parameters.

Results

The levels of plasma GDF11 in the COPD patients had significant positive correlations with the data of lung function. Furthermore, the levels of plasma GDF11 were significantly correlated with the physical activity, quadriceps strength, and exercise capacity. Moreover, the levels of plasma GDF11 were significantly correlated with the data of inflammatory markers. Although various factors were related to GDF11, the multiple regression analysis showed that physical activity was significantly associated with the levels of plasma GDF11.

Conclusion

Physical inactivity was significantly related to the decreased GDF11 levels in COPD, which might be useful for understanding the pathogenesis of COPD. Clarifying the relationships between the physical inactivity and GDF11 may reveal a potentially attractive therapeutic approach in COPD via increasing the plasma levels of GDF11.

Keywords:

• physical activity
• muscle strength
• rejuvenating factor
• COPD

Supplementary material

Figure S1 Levels of GDF11 in plasma.

Notes: Plasma was obtained from the control subjects, GOLD stage I/II and GOLD stage III/IV COPD patients. The levels of plasma GDF11 were investigated by immunoblotting (A). Ponceau S staining was used to evaluate the amounts of protein. The GDF11 levels were calculated by measuring the intensity of the bands (B). Open circles: control; closed circles (gray): GOLD stage I/II; closed circles (black): GOLD stage III/IV. Results are expressed mean ± SD. Data were analyzed with one-way ANOVA followed by Tukey’s test. ***p < 0.001 compared with control; +++p < 0.001 compared with GOLD stage I/II.

Abbreviations: ANOVA, analysis of variance; GDF11, growth differentiation factor 11; GOLD, Global Initiative for Chronic Obstructive Lung Disease; M, molecular weight marker.

Acknowledgments

We thank Dr Shunsuke Ito, Dr Koji Itakura, and Dr Ayumi Mitsune (Tohoku University Graduate School of Medicine, Miyagi, Japan) for recruiting patients and obtaining informed consent. We thank Mr Brent Bell for reading this manuscript. We thank Dr Taku Harada (Tohoku University Graduate School of Medicine, Miyagi, Japan) for help in measuring the quadriceps strength. We thank Dr Satoshi Miyata (Tohoku University Graduate School of Medicine, Miyagi, Japan) for his expert help with statistical analysis.

This study was supported by grants from the Japan Society for the Promotion of Science (grant number: #16H05307, #16K15453, #17H04180) and a grant from the Practical Research Project for Allergic Diseases and Immunology from Japan Agency for Medical Research and Development, AMED (grant number: #16ek0410018h0002, #16ek040036h0001, #17ek0410036h0002).

Author contributions

RT contributed to the recruiting of patients, obtaining informed consent, biochemical studies, data collection, and interpretation of results. HS designed the study and conducted the interpretation of results, provided technical advice, and writing of the manuscript. MY, AK, NF, SY, TO, and TT (Tsutomu Tamada) provided technical advice and interpretation of results. TI gave technical advice, contributed to interpretation of the results, and writing of the manuscript. KO, TN, KS, YK, HS, SY, MM, and TT (Tsuneyuki Takahashi) contributed to the recruitment of patients and obtaining informed consent. MI designed the study and contributed to the interpretation of results and writing of the manuscript. All authors contributed toward data analysis, drafting and revising the paper and agree to be accountable for all aspects of the work.

Disclosure

The authors report no conflicts of interest in this work.