Accelerated epithelial cell senescence in IPF and the inhibitory role of SIRT6 in TGF-β-induced senescence of human bronchial epithelial cells
| العنوان: | Accelerated epithelial cell senescence in IPF and the inhibitory role of SIRT6 in TGF-β-induced senescence of human bronchial epithelial cells |
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| المؤلفون: | Stephen L. Nishimura, Satoko Nojiri, Kazuyoshi Kuwano, Shunsuke Minagawa, Makoto Kawaishi, Jun Araya, Yoko Yumino, Makoto Odaka, Takanori Numata, Hiromichi Hara, Katsutoshi Nakayama, Toshiaki Morikawa |
| المصدر: | American Journal of Physiology-Lung Cellular and Molecular Physiology. 300:L391-L401 |
| بيانات النشر: | American Physiological Society, 2011. |
| سنة النشر: | 2011 |
| مصطلحات موضوعية: | Cyclin-Dependent Kinase Inhibitor p21, Pulmonary and Respiratory Medicine, Senescence, SIRT6, Proteasome Endopeptidase Complex, Physiology, Cellular differentiation, Interleukin-1beta, Bronchi, Biology, Transforming Growth Factor beta1, Fibrosis, Physiology (medical), medicine, Humans, Sirtuins, Myofibroblasts, Cellular Senescence, Interleukin, Cell Differentiation, Epithelial Cells, Articles, Cell Biology, respiratory system, beta-Galactosidase, medicine.disease, Idiopathic Pulmonary Fibrosis, respiratory tract diseases, Immunology, Cancer research, Protein Processing, Post-Translational, Cell aging, Myofibroblast, Transforming growth factor |
| الوصف: | Reepithelialization of remodeled air spaces with bronchial epithelial cells is a prominent pathological finding in idiopathic pulmonary fibrosis (IPF) and is implicated in IPF pathogenesis. Recent studies suggest that epithelial senescence is a risk factor for development of IPF, indicating such reepithelialization may be influenced by the acceleration of cellular senescence. Among the sirtuin (SIRT) family, SIRT6, a class III histone deacetylase, has been demonstrated to antagonize senescence. We evaluated the senescence of bronchiolization in association with SIRT6 expression in IPF lung. Senescence-associated β-galactosidase staining and immunohistochemical detection of p21 were performed to evaluate cellular senescence. As a model for transforming growth factor (TGF)-β-induced senescence of abnormal reepithelialization, we used primary human bronchial epithelial cells (HBEC). The changes of SIRT6, p21, and interleukin (IL)-1β expression levels in HBEC, as well as type I collagen expression levels in fibroblasts, were evaluated. In IPF lung samples, an increase in markers of senescence and SIRT6 expression was found in the bronchial epithelial cells lining cystically remodeled air spaces. We found that TGF-β induced senescence in primary HBEC by increasing p21 expression, and, whereas TGF-β also induced SIRT6, it was not sufficient to inhibit cellular senescence. However, overexpression of SIRT6 efficiently inhibited TGF-β-induced senescence via proteasomal degradation of p21. TGF-β-induced senescent HBEC secreted increased amounts of IL-1β, which was sufficient to induce myofibroblast differentiation in fibroblasts. These findings suggest that accelerated epithelial senescence plays a role in IPF pathogenesis through perpetuating abnormal epithelial-mesenchymal interactions, which can be antagonized by SIRT6. |
| تدمد: | 1522-1504 1040-0605 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::667dd876eec7ed7f88704f26ad106c0cTest https://doi.org/10.1152/ajplung.00097.2010Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....667dd876eec7ed7f88704f26ad106c0c |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15221504 10400605 |
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