Down-Regulation of Soluble α-Klotho is Associated with Reduction in Serum Irisin Levels in Chronic Obstructive Pulmonary Disease
Down-Regulation of Soluble α-Klotho is Associated with Reduction in Serum Irisin Levels in Chronic Obstructive Pulmonary Disease
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DOI：
10.1007/s00408-016-9870-7
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发表时间：
2016-06-01
期刊：
影响因子：
5
通讯作者：
Hirata, Kazuto
中科院分区：
文献类型：
--
作者：
Kureya, Yuko;Kanazawa, Hiroshi;Hirata, Kazuto
klotho基因最初被鉴定为一个假定的衰老抑制基因。Klotho耗尽的小鼠表现出缩短的寿命，并表现出各种过早衰老相关的表型，如肺气肿和肌肉减少症。为探讨分泌型klotho蛋白在慢性阻塞性肺疾病（COPD）中的作用，检测了16例非吸烟者、13例非COPD吸烟者和24例COPD吸烟者血清中α-klotho和鸢尾素水平。此外，我们研究了COPD吸烟者的可溶性α-klotho水平与肺功能测试、心肺运动测试（CPET）和骨骼肌功能结果之间的相关性，COPD吸烟者的可溶性α-klotho水平显著低于非吸烟者和非COPD吸烟者。在COPD吸烟者中，这些水平与肺功能检查的任何参数均无显著相关性。在CPET中，峰值VO 2与FEV 1（%预测值）（r = 0.76，p = 0.0003）和DLCO（%预测值）（r = 0.62，p = 0.003）显著相关。相反，可溶性α-klotho水平与峰值VO 2无显著相关性。患有COPD的吸烟者的鸢尾素水平也显著较低。此外，可溶性α-klotho与血清鸢尾素水平之间存在显著相关性（r = 0.61，p = 0.004）。我们的研究结果可以为了解可溶性α-klotho对COPD骨骼肌的影响提供关键的第一步，并可能导致识别用于治疗COPD的新分子靶点。
The klotho gene was originally identified as a putative aging-suppressor gene. Klotho-depleted mice display a shortened life span and exhibit a variety of premature aging-related phenotypes such as pulmonary emphysema and sarcopenia. This study was designed to determine the roles of secreted-type klotho protein on lung and skeletal muscle in chronic obstructive pulmonary disease (COPD).Serum alpha-klotho and irisin levels were assayed in 16 non-smokers, 13 smokers without COPD, and 24 smokers with COPD. Moreover, we examined correlations between soluble alpha-klotho levels and the results of lung function test, cardiopulmonary exercise test (CPET), and skeletal muscle function in smokers with COPD.Soluble alpha-klotho levels were significantly lower in smokers with COPD compared to non-smokers and smokers without COPD. In smokers with COPD, those levels did not significantly correlate with any parameters of lung function test. In CPET, peak VO2 significantly correlated with FEV1 (% predicted) (r = 0.76, p = 0.0003) and DLCO (% predicted) (r = 0.62, p = 0.003). In contrast, soluble alpha-klotho levels did not significantly correlate with peak VO2. Irisin levels were also significantly lower in smokers with COPD. Moreover, there was a significant correlation between soluble alpha-klotho and serum irisin levels (r = 0.61, p = 0.004).Our findings could provide a critical first step to understanding the impacts of soluble alpha-klotho on skeletal muscle in COPD and may lead to the identification of new molecular targets for the treatment of COPD.