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ITGB 4 deficiency induces senescence of airway epithelial cells through p53 activation
Author(s) -
Yuan Lin,
Du Xizi,
Tang Sha,
Wu Shuangyan,
Wang Leyuan,
Xiang Yang,
Qu Xiangping,
Liu Huijun,
Qin Xiaoqun,
Liu Chi
Publication year - 2019
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.14749
Subject(s) - senescence , respiratory epithelium , immunology , epithelium , oxidative stress , asthma , airway , microbiology and biotechnology , medicine , biology , cancer research , pathology , endocrinology , surgery
Aging is characterized by a progressive loss of physiological integrity, leading to impaired organ function and, ultimately, increased vulnerability to death. Many complex diseases are related to aging, including asthma. In the lung, the airway epithelium serves as the first barrier to prevent the access of inspired external stimuli and dictates the initial stress responses. Notably, in the airway mucosa of asthma patients, an increase in senescent airway epithelial cells has been detected. Although it has been speculated that the senescence of airway epithelial cells could increase asthma susceptibility and aggravate asthma severity, the role of cell senescence in the development of asthma remains unclear. Integrin β4 ( ITGB 4) is a structural adhesion molecule with complex physiological functions that is downregulated in airway epithelial cells of asthma patients. This study demonstrates that the expression of ITGB 4 in airway epithelial cells is downregulated significantly under oxidative stress or upon inflammatory stimulation. Moreover, we show that ITGB 4 deficiency induces the senescence of airway epithelial cells through the activation of the p53 pathway both in vitro and in vivo . Together, our results demonstrate that airway epithelial senescence induced by ITGB 4 deficiency after oxidative stress or inflammatory stimulation may be involved in the pathogenesis of asthma. Understanding the contribution of ITGB 4 deficiency to the senescence of airway epithelial cells in asthma patients may provide new therapeutic approaches for the treatment of asthma.