27-Hydroxycholesterol accelerates cellular senescence in human lung resident cells
| Autor: | Tadahisa Numakura, Yuichiro Hashimoto, Akira Koarai, Tsutomu Tamada, Tomohiro Ichikawa, Kei Sato, Tatsuma Okazaki, Mitsuhiro Yamada, Rie Tanaka, Kyoko Abe, Takashi Kikuchi, Satoru Yanagisawa, Toshiaki Kikuchi, Shinsaku Togo, Hisatoshi Sugiura, Yasushi Hoshikawa, Katsuhiro Onodera, Yoshinori Okada, Masakazu Ichinose |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Pulmonary and Respiratory Medicine Senescence Physiology Biology Cell Line Pathogenesis Pulmonary Disease Chronic Obstructive 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation Physiology (medical) Macrophages Alveolar medicine Humans Lung Cellular Senescence Cyclin-Dependent Kinase Inhibitor p16 Cell Proliferation COPD Cell growth Epithelial Cells Cell Biology Fibroblasts respiratory system medicine.disease Reactive Nitrogen Species Hydroxycholesterols respiratory tract diseases 030104 developmental biology medicine.anatomical_structure 030228 respiratory system Cell culture Immunology Cholestanetriol 26-Monooxygenase sense organs Tumor Suppressor Protein p53 Signal transduction Signal Transduction |
| Zdroj: | American Journal of Physiology-Lung Cellular and Molecular Physiology. 310:L1028-L1041 |
| ISSN: | 1522-1504 1040-0605 |
| DOI: | 10.1152/ajplung.00351.2015 |
| Popis: | Cellular senescence is reportedly involved in the pathogenesis of chronic obstructive pulmonary disease (COPD). We previously showed that 27-hydroxycholesterol (27-OHC) is elevated in the airways of COPD patients compared with those in healthy subjects. The aim of this study was to investigate whether lung fibroblasts of COPD patients are senescent and to determine the effects of 27-OHC on senescence of lung resident cells, including fibroblasts and airway epithelial cells. Localization of senescence-associated proteins and sterol 27-hydroxylase was investigated in the lungs of COPD patients by immunohistochemical staining. To evaluate whether 27-OHC accelerates cellular senescence, lung resident cells were exposed to 27-OHC. Senescence markers and fibroblast-mediated tissue repair were investigated in the 27-OHC-treated cells. Expression of senescence-associated proteins was significantly enhanced in lung fibroblasts of COPD patients. Similarly, expression of sterol 27-hydroxylase was significantly upregulated in lung fibroblasts and alveolar macrophages in these patients. Treatment with the concentration of 27-OHC detected in COPD airways significantly augmented expression of senescence-associated proteins and senescence-associated β-galactosidase activity, and delayed cell growth through the prostaglandin E2-reactive nitrogen species pathway. The 27-OHC-treated fibroblasts impaired tissue repair function. Fibroblasts from lungs of COPD patients showed accelerated senescence and were more susceptible to 27-OHC-induced cellular senescence compared with those of healthy subjects. In conclusion, 27-OHC accelerates cellular senescence in lung resident cells and may play a pivotal role in cellular senescence in COPD. |
| Databáze: | OpenAIRE |
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