Ryo Okuda1, Kazutetsu Aoshiba2, Hidekazu Matsushima3, Takashi Ogura1, Koji Okudela4, Kenichi Ohashi4. 1. Department of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center, Yokohama, Japan. 2. Department of Respiratory Medicine, Tokyo Medical University Ibaraki Medical Center, Inashiki, Japan. 3. Department of Respiratory Medicine, Saitama Red Cross Hospital, Saitama, Japan. 4. Department of Pathology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
Abstract
BACKGROUND: The senescence-associated secretory phenotype (SASP) develops due to cellular senescence during conditions such as chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF). However, studies comparing the degree of cellular senescence and SASP between COPD and IPF are limited. Furthermore, to the best of our knowledge, no study has examined cellular senescence and/or SASP in connective tissue disease-associated interstitial lung disease (CTD-ILD). METHODS: To compare the degree of cellular senescence among COPD, IPF, and CTD-ILD, tissue samples from surgical lung biopsies or noncancerous tissue from lobectomy specimens of patients with lung cancer were subjected to immunostaining for p16 and p21. Double-staining for p16 and phosphorylated NF-κB was performed to verify the relationship between cellular senescence and SASP. RESULTS: There was a greater degree of enhancement of p16 and p21 expression in patients with IPF than in those with COPD and controls. Immunostaining for p16 revealed an enhanced expression of this marker in patients with COPD compared with that in controls. No significant differences were observed in the phosphorylated NF-κB expression rate of p16-positive and p16-negative cells among patients with IPF, CTD-ILD, and COPD. CONCLUSIONS: Epithelial cells in patients with IPF express higher levels of both cellular senescence and SASP than those in patients with COPD or controls.
BACKGROUND: The senescence-associated secretory phenotype (SASP) develops due to cellular senescence during conditions such as chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF). However, studies comparing the degree of cellular senescence and SASP between COPD and IPF are limited. Furthermore, to the best of our knowledge, no study has examined cellular senescence and/or SASP in connective tissue disease-associated interstitial lung disease (CTD-ILD). METHODS: To compare the degree of cellular senescence among COPD, IPF, and CTD-ILD, tissue samples from surgical lung biopsies or noncancerous tissue from lobectomy specimens of patients with lung cancer were subjected to immunostaining for p16 and p21. Double-staining for p16 and phosphorylated NF-κB was performed to verify the relationship between cellular senescence and SASP. RESULTS: There was a greater degree of enhancement of p16 and p21 expression in patients with IPF than in those with COPD and controls. Immunostaining for p16 revealed an enhanced expression of this marker in patients with COPD compared with that in controls. No significant differences were observed in the phosphorylated NF-κB expression rate of p16-positive and p16-negative cells among patients with IPF, CTD-ILD, and COPD. CONCLUSIONS: Epithelial cells in patients with IPF express higher levels of both cellular senescence and SASP than those in patients with COPD or controls.
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