Airway basal stem cells: a perspective on their roles in epithelial homeostasis and remodeling

Abstract

The small airways of the human lung undergo pathological changes in pulmonary disorders, such as chronic obstructive pulmonary disease (COPD), asthma, bronchiolitis obliterans and cystic fibrosis. These clinical problems impose huge personal and societal healthcare burdens. The changes, termed 'pathological airway remodeling' , affect the epithelium, the underlying mesenchyme and the reciprocal trophic interactions that occur between these tissues. Most of the normal human airway is lined by a pseudostratified epithelium of ciliated cells, secretory cells and 6-30% basal cells, the proportion of which varies along the proximal-distal axis. Epithelial abnormalities range from hypoplasia (failure to differentiate) to basal-and goblet-cell hyperplasia, squamous-and goblet-cell metaplasia, dysplasia and malignant transformation. Mesenchymal alterations include thickening of the basal lamina, smooth muscle hyperplasia, fibrosis and inflammatory cell accumulation. Paradoxically, given the prevalence and importance of airway remodeling in lung disease, its etiology is poorly understood. This is due, in part, to a lack of basic knowledge of the mechanisms that regulate the differentiation, maintenance and repair of the airway epithelium. Specifically, little is known about the proliferation and differentiation of basal cells, a multipotent stem cell population of the pseudostratified airway epithelium. This Perspective summarizes what we know, and what we need to know, about airway basal cells to evaluate their contributions to normal and abnormal airway remodeling. We contend that exploiting well-described model systems using both human airway epithelial cells and the pseudostratified epithelium of the genetically tractable mouse trachea will enable crucial discoveries regarding the pathogenesis of airway disease.

Evidence for multiple roles for grainyhead-like 2 in the establishment and maintenance of human mucociliary airway epithelium

“…This suggests that we have uncovered a set of genes that could potentially mediate important functions relevant to airway health and disease. One strategy to define these functions will be to conditionally manipulate them in the mouse trachea, a model for the human mucociliary epithelium with basal cells (1).…”

“…Most of the conducting airways of the human lung are lined by an epithelium made up of ciliated and secretory luminal cells and undifferentiated basal progenitors (1,2). This layer fulfills many critical physiological functions, including mucociliary clearance and innate host defense, and provides a barrier against pathogens and allergens.…”

Erratum: Non-small-cell lung cancers: a heterogeneous set of diseases

“…ADCs often have glandular histology and express biomarkers that are consistent with an origin in the distal lung, including thyroid transcription factor 1 (TTF1; also known as NKX2-1) and keratin 7 (KRT7) 4,5 . By contrast, SCCs are characterized by squamous differentiation, which is more reminiscent of the pseudostratified columnar epithelium that lines the trachea and upper airways 4,6 . SCCs are distinguished from ADCs in the clinic by immunostaining for cytokeratin 5 and cyto keratin 6 and/or the transcription factors SRY-box 2 (SOX2) and p63 (REFS 4,5,7).…”

Claudins in Normal and Lung Cancer State

“…Epithelial cells throughout of airway show major functions such as protection (Ciliated cells), progenitor cells (Basal and Clara cells), exocrine secretion (Goblet, Clara and Alveolar type II cells), endocrine secretion (Neuroendocrine pulmonary cells), and gas exchange (Alveolar type I cells) (Table 1) (Herzog, et al, 2008;Linnoila, 2006;Maeda, et al, 2007;Reynolds, et al, 2007;Rock, et al, 20010;Rogers, 2007 Herzog, et al, 2008;Linnoila, 2006;Maeda, et al, 2007;Reynolds, et al, 2007;Rock, et al, 2010;Rogers, 2007.…”

“…It is know that www.intechopen.com several physiopathological conditions could modify the lung epithelial cell pattern such as infection, cytokines, inflammatory mediators, pollutants and injury that are associated with common airway diseases, including chronic obstructive pulmonary disease, asthma, cystic fibrosis and cancer (Ballaz & Mulshine, 2003;Maeda, et al, 2007;Rock, et al, 2010).…”