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ID 116252
Oniki, Kentaro Kumamoto University
Nohara, Hirofumi Kumamoto University
Nakashima, Ryunosuke Kumamoto University
Obata, Yui Kumamoto University
Muto, Narumi Kumamoto University
Sakamoto, Yuki Kumamoto University
Ueno-Shuto, Keiko Sojo University
Imafuku, Tadashi Kumamoto University
Watanabe, Hiroshi Kumamoto University
Maruyama, Toru Kumamoto University
Otake, Koji Japanese Red Cross Kumamoto Health Care Center
Ogata, Yasuhiro Japanese Red Cross Kumamoto Health Care Center
Suico, Mary Ann Kumamoto University
Kai, Hirofumi Kumamoto University
Shuto, Tsuyoshi Kumamoto University
Saruwatari, Junji Kumamoto University
Content Type
Journal Article
Oxidative stress and inflammation play a key role in the age-related decline in the respiratory function. Adipokine in relation to the metabolic and inflammatory systems is attracting growing interest in the field of respiratory dysfunction. The present clinical and experimental studies investigated the role of the disulfide bond-forming oxidoreductase A-like protein (DsbA-L) gene, which has antioxidant and adiponectin multimeric (i.e. activation) properties, on the respiratory function of the elderly. We performed a retrospective longitudinal genotype-phenotype relationship analysis of 318 Japanese relatively elderly participants (mean age ± standard deviation: 67.0 ± 5.8 years) during a health screening program and an in vitro DsbA-L knock-down evaluation using 16HBE14o-cells, a commonly evaluated human airway epithelial cell line. The DsbA-L rs1917760 polymorphism was associated with a reduction in the ratio of forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) and %FEV1 and with the elevation of the prevalence of FEV1/FVC < 70%. We also confirmed that the polymorphism was associated with a decreased respiratory function in relation to a decrease in the ratio of high-molecular-weight adiponectin/total adiponectin (as a marker of adiponectin multimerization) and an increase in the oxidized human serum albumin (as an oxidative stress marker). Furthermore, we clarified that DsbA-L knock-down induced oxidative stress and up-regulated the mucus production in human airway epithelial cells. These findings suggest that the DsbA-L gene may play a role in protecting the respiratory function of the elderly, possibly via increased systemic adiponectin functions secreted from adipocytes or through systemic and/or local pulmonary antioxidant properties.
Journal Title
Scientific Reports
Springer Nature
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Pharmaceutical Sciences