Progenitor Cells in Proximal Airway Epithelial Development and Regeneration

Lynch, Thomas J.; Engelhardt, John F.

doi:10.1002/jcb.24834

Cited by 38 publications

(43 citation statements)

References 49 publications

(108 reference statements)

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“…1F′). In general, myoepithelial cells surround the glandular serous acini and the mucous tubules but not the glandular ducts [39]. ChAT-eGFP cells were not observed in parts of the submucosal glands containing α-SMA-positive myoepithelia (Fig.…”

Section: Cholinergic Epithelial Cells In the Airway Submucosal Glandmentioning

confidence: 92%

Identification of cholinergic chemosensory cells in mouse tracheal and laryngeal glandular ducts

Krasteva‐Christ

Soultanova

Schütz

et al. 2015

International Immunopharmacology

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Section: Cholinergic Epithelial Cells In the Airway Submucosal Glandmentioning

confidence: 92%

Identification of cholinergic chemosensory cells in mouse tracheal and laryngeal glandular ducts

Krasteva‐Christ

Soultanova

Schütz

et al. 2015

International Immunopharmacology

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“…Submucosal glands consist of two compartments: ducts and acini. Ducts are tubular tissues that connect acini to the surface epithelium (Liu and Engelhardt, 2008;Lynch and Engelhardt, 2014). The epithelium in the ducts is very similar to the surface epithelium, including the presence of basal, secretory and ciliated cell types.…”

Section: Submucosal Glandsmentioning

confidence: 99%

“…Developmentally, the appearance of submucosal glands varies from species to species. For example, in mice, submucosal gland primordium first appears on postnatal day 1, whereas in humans, submucosal gland placodes first appear during the third trimester (Lynch and Engelhardt, 2014). In addition to the differences in their relative developmental timing, the abundance and the location of submucosal glands vary between rodents and other mammals.…”

Section: Submucosal Glandsmentioning

confidence: 99%

“…Such plasticity has often been referred to as transdifferentiation, although when one stem cell converts into another, the appropriate terminology with reference to historical usage is transdetermination (Tata and Rajagopal, 2016a). Earlier studies have suggested that submucosal gland duct cells proliferate and migrate to repopulate the damaged pseudostratified surface epithelium following severe injury (Duan et al, 1998;Lynch and Engelhardt, 2014). Recent studies have also suggested that submucosal gland ductal basal cells can regenerate proximal airway epithelium following hypoxic ischemic injury (Hegab et al, 2011(Hegab et al, , 2012.…”

Section: Transdifferentiation and Transdetermination Of Airway Cellsmentioning

confidence: 99%

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Plasticity in the lung: making and breaking cell identity

2017

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In contrast to a prior emphasis on the finality of cell fate decisions in developmental systems, cellular plasticity is now emerging as a general theme in the biology of multiple adult organ systems. In the lung, lineage tracing has been used to identify distinct epithelial stem and progenitor cell populations. These cells, together with their differentiated progeny, maintain a stable identity during steady state conditions, but can display remarkable lineage plasticity following injury. This Review summarizes our current understanding of the different cell lineages of the adult mammalian lung and their responses to injury. In the lung, which is constantly exposed to infection and aerosolized toxins, epithelial plasticity might be more of a rule than an exception, and it is likely that different injuries elicit different facultative responses.

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“…Submucosal glands (SMGs) are secretory structures in cartilaginous airways that play important roles in airway innate immunity and also serve as a niche for airway stem cells (1)(2)(3). SMGs secrete the majority of mucus and fluid that coats the airways (4), which must be rapidly equilibrated to the proper pericellular liquid height for effective mucociliary transport (5).…”

mentioning

confidence: 99%

Glandular Proteome Identifies Antiprotease Cystatin C as a Critical Modulator of Airway Hydration and Clearance

Evans¹,

Joo

Keiser³

et al. 2016

Am J Respir Cell Mol Biol

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Defects in the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel lead to viscous secretions from submucosal glands that cannot be properly hydrated and cleared by beating cilia in cystic fibrosis (CF) airways. The mechanisms by which CFTR, and the predominant epithelial sodium channel (ENaC), control the hydration and clearance of glandular secretions remain unclear. We used a proteomics approach to characterize the proteins contained in CF and non-CF submucosal gland fluid droplets and found that differentially regulated proteases (cathepsin S and H) and their antiprotease (cystatin C) influenced the equilibration of fluid on the airway surface and tracheal mucociliary clearance (MCC). Contrary to prevailing models of airway hydration and clearance, cystatin C, or raising the airway surface liquid (ASL) pH, inhibited cathepsindependent ENaC-mediated fluid absorption and raised the height of ASL, and yet decreased MCC velocity. Importantly, coupling of both CFTR and ENaC activities were required for effective MCC and for effective ASL height equilibration after volume challenge. Cystatin C-inhibitable cathepsins controlled initial phases of ENaC-mediated fluid absorption, whereas CFTR activity was required to prevent ASL dehydration. Interestingly, CF airway epithelia absorbed fluid more slowly owing to reduced cysteine protease activity in the ASL but became abnormally dehydrated with time. Our findings demonstrate that, after volume challenge, pH-dependent protease-mediated coupling of CFTR and ENaC activities are required for rapid fluid equilibration at the airway surface and for effective MCC. These findings provide new insights into how glandular fluid secretions may be equilibrated at the airway surface and how this process may be impaired in CF.Keywords: cystic fibrosis; airway clearance; cystic fibrosis transmembrane conductance regulator; epithelial sodium channel; submucosal glands Clinical RelevanceAirway submucosal glands play an important role in cystic fibrosis (CF) lung disease. Using a proteomics approach to study pure glandular secretions from CF and non-CF human samples, we identified dysregulated proteases and antiproteases that impact airway clearance and airway surface liquid homeostasis. We demonstrate that cysteine proteases and the antiprotease cystatin C regulate pH-dependent protease coupling of CF transmembrane conductance regulator and epithelial sodium channel activities that allow for rapid fluid equilibration at the airway surface required for effective mucociliary clearance.

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Progenitor Cells in Proximal Airway Epithelial Development and Regeneration

Cited by 38 publications

References 49 publications

Identification of cholinergic chemosensory cells in mouse tracheal and laryngeal glandular ducts

Identification of cholinergic chemosensory cells in mouse tracheal and laryngeal glandular ducts

Plasticity in the lung: making and breaking cell identity

Glandular Proteome Identifies Antiprotease Cystatin C as a Critical Modulator of Airway Hydration and Clearance

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