Aberrant Epithelial Cell Proliferation in Peripheral Airways in Bronchiectasis

Peng, Yang; Xu, Ai-Ru; Chen, Shiying; Huang, Yan; Han, Xiaorong; Guan, Weijun; Wang, Deyun; Zhong, Nanshan

doi:10.3389/fcell.2020.00088

Cited by 8 publications

(3 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Histopathological analysis revealed areas of denuded ciliated epithelium, as well as goblet cell hyperplasia, as common features of the asthmatic airway [10,62]. In addition, bronchiectasis biopsies showed extensive epithelial hyperplasia, with reduced lung progenitor cells, and an enhanced number of self-renewing cells capable of differentiation into ciliated and secretory cells [63]. Such observations may suggest that aberrant epithelial repair mechanisms contribute to the pathophysiology of asthma with associated bronchiectasis.…”

Section: A Fumigatus-induced Epithelial Cell Damagementioning

confidence: 88%

Aspergillus fumigatus—Host Interactions Mediating Airway Wall Remodelling in Asthma

Namvar

Labram

Rowley

et al. 2022

JoF

View full text Add to dashboard Cite

Asthma is a chronic heterogeneous respiratory condition that is mainly associated with sensitivity to airborne agents such as pollen, dust mite products and fungi. Key pathological features include increased airway inflammation and airway wall remodelling. In particular, goblet cell hyperplasia, combined with excess mucus secretion, impairs clearance of the inhaled foreign material. Furthermore, structural changes such as subepithelial fibrosis and increased smooth muscle hypertrophy collectively contribute to deteriorating airway function and possibility of exacerbations. Current pharmacological therapies focused on airway wall remodelling are limited, and as such, are an area of unmet clinical need. Sensitisation to the fungus, Aspergillus fumigatus, is associated with enhanced asthma severity, bronchiectasis, and hospitalisation. How Aspergillus fumigatus may drive airway structural changes is unclear, although recent evidence points to a central role of the airway epithelium. This review provides an overview of the airway pathology in patients with asthma and fungal sensitisation, summarises proposed airway epithelial cell–fungal interactions and discusses the initiation of a tissue remodelling response. Related findings from in vivo animal models are included given the limited analysis of airway pathology in patients. Lastly, an important role for Aspergillus fumigatus-derived proteases in triggering a cascade of damage-repair events through upregulation of airway epithelial-derived factors is proposed.

show abstract

Section: A Fumigatus-induced Epithelial Cell Damagementioning

confidence: 88%

Aspergillus fumigatus—Host Interactions Mediating Airway Wall Remodelling in Asthma

Namvar

Labram

Rowley

et al. 2022

JoF

View full text Add to dashboard Cite

show abstract

“…The abnormal airway epithelium contributes to both CF and bronchiectasis ( Peng et al, 2020 ; Chen et al, 2018 ; Barbry et al, 2020 ). Insufficient growth and differentiation of epithelial cells can lead to persistent mucosal injury that promotes bacterial colonization and neutrophilic inflammation.…”

Section: Lncrna–mirna Interaction In Chronic Inflammatory Airway Dise...mentioning

confidence: 99%

The Novel Regulatory Role of the lncRNA–miRNA–mRNA Axis in Chronic Inflammatory Airway Diseases

Qiao

Hou

et al. 2022

Front. Mol. Biosci.

View full text Add to dashboard Cite

Chronic inflammatory airway diseases, characterized by airway inflammation and airway remodelling, are increasing as a cause of morbidity and mortality for all age groups and races across the world. The underlying molecular mechanisms involved in chronic inflammatory airway diseases have not been fully explored. MicroRNAs (miRNAs) and long noncoding RNAs (lncRNAs) have recently attracted much attention for their roles in the regulation of a variety of biological processes. A number of studies have confirmed that both lncRNAs and miRNAs can regulate the initiation and progression of chronic airway diseases by targeting mRNAs and regulating different cellular processes, such as proliferation, apoptosis, inflammation, migration, and epithelial–mesenchymal transition (EMT). Recently, accumulative evidence has shown that the novel regulatory mechanism underlying the interaction among lncRNAs, miRNAs and messenger RNAs (mRNAs) plays a critical role in the pathophysiological processes of chronic inflammatory airway diseases. In this review, we comprehensively summarized the regulatory roles of the lncRNA–miRNA–mRNA network in different cell types and their potential roles as biomarkers, indicators of comorbidities or therapeutic targets for chronic inflammatory airway diseases, particularly chronic obstructive pulmonary disease (COPD) and asthma.

show abstract

“…Rao et al found that abnormal ABSCs in COPD resulted in pathologic characteristics including airway fibrosis, inflammation, and mucus hypersecretion [ 7 ]. Peng et al reported that airway progenitor cells were abnormally proliferative in bronchiectasis [ 8 ]. Moreover, growing evidence indicates that the dysfunction of ABSCs plays a crucial role in driving the progression of idiopathic pulmonary fibrosis [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

Mechanical stretch promotes apoptosis and impedes ciliogenesis of primary human airway basal stem cells

Lin,

Zeng,

Luo

et al. 2023

Respir Res

View full text Add to dashboard Cite

Background Airway basal stem cells (ABSCs) have self-renewal and differentiation abilities. Although an abnormal mechanical environment related to chronic airway disease (CAD) can cause ABSC dysfunction, it remains unclear how mechanical stretch regulates the behavior and structure of ABSCs. Here, we explored the effect of mechanical stretch on primary human ABSCs. Methods Primary human ABSCs were isolated from healthy volunteers. A Flexcell FX-5000 Tension system was used to mimic the pathological airway mechanical stretch conditions of patients with CAD. ABSCs were stretched for 12, 24, or 48 h with 20% elongation. We first performed bulk RNA sequencing to identify the most predominantly changed genes and pathways. Next, apoptosis of stretched ABSCs was detected with Annexin V-FITC/PI staining and a caspase 3 activity assay. Proliferation of stretched ABSCs was assessed by measuring MKI67 mRNA expression and cell cycle dynamics. Immunofluorescence and hematoxylin-eosin staining were used to demonstrate the differentiation state of ABSCs at the air-liquid interface. Results Compared with unstretched control cells, apoptosis and caspase 3 activation of ABSCs stretched for 48 h were significantly increased (p < 0.0001; p < 0.0001, respectively), and MKI67 mRNA levels were decreased (p < 0.0001). In addition, a significant increase in the G0/G1 population (20.2%, p < 0.001) and a significant decrease in S-phase cells (21.1%, p < 0.0001) were observed. The ratio of Krt5+ ABSCs was significantly higher (32.38% vs. 48.71%, p = 0.0037) following stretching, while the ratio of Ac-tub+ cells was significantly lower (37.64% vs. 21.29%, p < 0.001). Moreover, compared with the control, the expression of NKX2-1 was upregulated significantly after stretching (14.06% vs. 39.51%, p < 0.0001). RNA sequencing showed 285 differentially expressed genes, among which 140 were upregulated and 145 were downregulated, revealing that DDIAS, BIRC5, TGFBI, and NKX2-1 may be involved in the function of primary human ABSCs during mechanical stretch. There was no apparent difference between stretching ABSCs for 24 and 48 h compared with the control. Conclusions Pathological stretching induces apoptosis of ABSCs, inhibits their proliferation, and disrupts cilia cell differentiation. These features may be related to abnormal regeneration and repair observed after airway epithelium injury in patients with CAD.

show abstract

Aberrant Epithelial Cell Proliferation in Peripheral Airways in Bronchiectasis

Cited by 8 publications

References 34 publications

Aspergillus fumigatus—Host Interactions Mediating Airway Wall Remodelling in Asthma

Aspergillus fumigatus—Host Interactions Mediating Airway Wall Remodelling in Asthma

The Novel Regulatory Role of the lncRNA–miRNA–mRNA Axis in Chronic Inflammatory Airway Diseases

Mechanical stretch promotes apoptosis and impedes ciliogenesis of primary human airway basal stem cells

Contact Info

Product

Resources

About