S65 Large and small airway epithelial cell senescence present in COPD and bronchiectasis?

The continuous conversion of soluble fibronectin into extracellular matrix fibrils occurs through a dynamic, cell-dependent process. As the extracellular matrix is assembled, changes in the conformation of matrix proteins may expose biologically active, matricryptic sites that alter cell behavior. In this study, an in vitro model of wound healing was used to determine the role of matrix fibronectin in airway epithelial cell motility. Our findings indicate that, under basal conditions, small airway epithelial cell (SAEC) migration requires active fibronectin matrix polymerization. Furthermore, SAEC migration is increased significantly by the interaction of cells with a recombinant construct containing fibronectin's matricryptic III-1 site. In contrast, addition of increasing amounts of fibronectin to SAECs significantly decreased the rate of cell migration. This fibronectin-induced inhibition of cell migration was overcome by blocking excess fibronectin matrix deposition. These data indicate that SAEC migration is regulated in a biphasic manner by the polymerization of fibronectin in the extracellular matrix and suggest a stimulatory role for fibronectin's matricryptic III-1 site in cell motility.

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Effects Of Licorice Flavonoids And Liquiritin Apioside On Cigarette Smoke Extract Induced Cell Toxicity, IL-8 And MUC5AC MRNA Expression In The Human Small Airway Epithelial Cell NCI-H292

10.1164/ajrccm-conference.2010.181.1_meetingabstracts.a4964 ◽

2010 ◽

Author(s):

Fen-fen Li ◽

Xin-wei Dong ◽

Guan Yan ◽

Qiang-min Xie

Keyword(s):

Epithelial Cell ◽

Mrna Expression ◽

Cigarette Smoke ◽

Airway Epithelial Cell ◽

Cigarette Smoke Extract ◽

Small Airway ◽

Airway Epithelial ◽

Cell Toxicity ◽

Small Airway Epithelial Cell

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The Function of Ophiocordyceps sinensis in Airway Epithelial Cell Senescence in a Rat COPD Model

Canadian Respiratory Journal ◽

10.1155/2018/6080348 ◽

2018 ◽

Vol 2018 ◽

pp. 1-9

Author(s):

Xiaohui Ma ◽

Xingai Jiao ◽

Jinxiang Wu ◽

Jiping Zhao ◽

Yurong Xu ◽

...

Keyword(s):

Epithelial Cell ◽

Quantitative Pcr ◽

Airway Epithelial Cell ◽

Cell Senescence ◽

Airway Epithelial ◽

Airway Epithelia ◽

Real Time Quantitative Pcr ◽

Ophiocordyceps Sinensis

Ophiocordyceps sinensis (O. sinensis) seems to be able to alleviate airway epithelial cell senescence in chronic obstructive pulmonary disease (COPD). The objective of the study is to evaluate the effect of O. sinensis on airway epithelial senescence in the COPD model both in vitro and in vivo. We observed the expression of P16 and P21 in the airway epithelia of 30 patients with COPD. The optimal concentration of O. sinensis and exposure time of the cigarette smoke extract (CSE) were determined in vitro, and senescence-associated β-galactosidase (SA-β-gal) and 5-bromodeoxyuridine (BrdU) were used to evaluate the senescence and proliferation of human bronchial epithelial (16HBE) cells pretreated with O. sinensis by staining kits. COPD model rats were treated with O. sinensis at various concentrations to determine the changes in P16 and P21 expression in airway epithelial tissues. It was found that the expression levels of P16 and P21 were higher in the airway epithelia of COPD patients than those in the control group based on immunohistochemical staining, real-time quantitative PCR, and western blotting. The CSE could induce 16HBE cell senescence, and O. sinensis could alleviate CSE-induced senescence and promote the proliferation of 16HBE cells. The expression levels of P16 and P21 were also higher in the airway epithelia of COPD model rats; however, the levels of P16 and P21 in the groups treated with all concentrations of O. sinensis were obviously lower than those in the COPD model group based on real-time quantitative PCR and western blotting. In conclusion, the CSE can induce airway epithelium senescence, and O. sinensis can inhibit CSE-induced cellular senescence, both in vitro and in vivo.

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Effective-Component Compatibility of Bufei Yishen Formula Ⅲ Ameliorated COPD By Improving Airway Epithelial Cell Senescence Via Promoting Mitophagy By Nrf2/PINK1 Pathway

10.21203/rs.3.rs-1198975/v1 ◽

2022 ◽

Author(s):

Min-yan Li ◽

Yan-qin Qin ◽

Jian-sheng Li ◽

Peng Zhao ◽

Yan-ge Tian ◽

...

Keyword(s):

Oxidative Stress ◽

Epithelial Cell ◽

Epithelial Cells ◽

Airway Epithelial Cell ◽

Airway Epithelial Cells ◽

Cell Senescence ◽

Chronic Obstructive ◽

Airway Epithelial ◽

Positive Effects ◽

Effective Component

Abstract Background: Effective-component compatibility of Bufei Yishen formula Ⅲ (ECC-BYF Ⅲ) shows positive effects on stable chronic obstructive pulmonary disease (COPD).Purpose: To investigate the mechanisms of ECC-BYF Ⅲ on COPD rats from the aspect of airway epithelial cell senescence.Methods: COPD model rats were treated with ECC-BYF Ⅲ for 8 weeks and the efficacy was evaluated. Cigarette smoke extract (CSE) induced senescence model of airway epithelial cells were treated with ECC-BYF Ⅲ, the related enzymes and proteins involved in oxidative stress and mitophagy were detected.Results: ECC-BYF Ⅲ markedly rescued pulmonary function and histopathological changes, which might be associated with the amelioration of lung senescence, including reduction of malondialdehyde (MDA) and tumor necrosis factor-α (TNF-α), interleukin (IL)-6 and matrix metalloproteinase (MMP)-9, increase of the level of total superoxide dismutase (T-SOD), and decease of p21 level in airway. Furthermore, ECC-BYF Ⅲ suppressed p16, p21 expressions and senescence-associated β-galactosidase (SA-β-Gal) in CSE-induced airway epithelial cells. Moreover, ECC-BYF Ⅲ upregulated the mitophagy-related proteins, including co-localization of TOM20 and LC3B, PINK1, PARK2, and improved mitochondrial function with upregulating mitochondrial mitofusin (Mfn)2 and reducing dynamin-related protein 1 (Drp1) expression. ECC-BYF Ⅲ enhanced the activities of T-SOD and GSH-PX by up-regulating Nrf2, thus inhibiting oxidative stress. After intervention with Nrf2 inhibitor, the regulation effects of ECC-BYF Ⅲ on oxidative stress, mitophagy and senescence in airway epithelial cells were significantly suppressed.Conclusions: ECC-BYF Ⅲ exerts beneficial effects on COPD rats by ameliorating airway epithelial cell senescence, which is mediated by inhibiting oxidative stress and subsequently enhancing mitophagy through activation of Nrf2 signaling.

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