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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 of 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 (ITGB4) is a structural adhesion molecule with complex physiological functions that is down-regulated in airway epithelial cells of asthma patients. This study demonstrates that the expression of ITGB4 in airway epithelial cells is down-regulated significantly under oxidative stress or upon inflammatory stimulation. Moreover, we show that ITGB4 deficiency induces the senescence of airway epithelial cells through the activation of p53 pathway both in vitro and in vivo. Together, our results demonstrate that airway epithelial senescence induced by ITGB4 deficiency after oxidative stress or inflammatory stimulation may be involved in the pathogenesis of asthma. Understanding the contribution of ITGB4 deficiency to the senescence of airway epithelial cells in asthma patients may provide new therapeutic approaches for the treatment of asthma. This article is protected by copyright. All rights reserved.
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Name: The FEBS journal
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Process by which cells irreversibly stop dividing and enter a state of permanent growth arrest without undergoing CELL DEATH. Senescence can be induced by DNA DAMAGE or other cellular stresses, such as OXIDATIVE STRESS.
A form of bronchial disorder with three distinct components: airway hyper-responsiveness (RESPIRATORY HYPERSENSITIVITY), airway INFLAMMATION, and intermittent AIRWAY OBSTRUCTION. It is characterized by spasmodic contraction of airway smooth muscle, WHEEZING, and dyspnea (DYSPNEA, PAROXYSMAL).
A cell adhesion molecule that is expressed on the membranes of nearly all EPITHELIAL CELLS, especially at the junctions between intestinal epithelial cells and intraepithelial LYMPHOCYTES. It also is expressed on the surface of ADENOCARCINOMA and epithelial tumor cells. It may function in the MUCOSA through homophilic interactions to provide a barrier against infection. It also regulates the proliferation and differentiation of EMBRYONIC STEM CELLS.
The system of ACETYLCHOLINE-synthesizing enzymes, transporters, receptors and degrading enzymes that characterize non-neuronal cholinergic cells such as airway and skin EPITHELIAL CELLS.
An anoctamin chloride channel expressed at high levels in the liver, skeletal muscle, and gastrointestinal muscles that functions in transepithelial anion transport and smooth muscle contraction. It is essential for the function of the INTERSTITIAL CELLS OF CAJAL and plays a major role in chloride conduction by airway epithelial cells and in tracheal cartilage development.
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