Detection and inhibition of ENaC-activating proteases associated with airway dehydration in COPD

Martin, S. Lorraine; Reihill, James; Douglas, Lisa; Ferguson, Timothy; Walker, Brian K.

doi:10.1183/1393003.congress-2017.pa4933

Cited by 1 publication

(2 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Significantly elevated levels of both cell-attached and soluble tryptic activity have also been reported in CuFi-1 (CF Phe508del cell line) compared with NuLi-1 (non-CF) controls [71]. Similarly, COPD airway epithelial cells were found to secrete ~40% more TLP activity than healthy cell controls, which may contribute to an enhanced ENaC activity in this disease [72]. Optimal ASL hydration is also regulated by ENaC-dependent sodium and fluid absorption working in tandem with cystic fibrosis transmembrane conductance regulator (CFTR) chloride secretion across the apical membrane of epithelial cells.…”

Section: Over-activation Of Enac Leads To Airways Dehydration and Impaired Mucociliary Clearance Mechanisms In Mucoldsmentioning

confidence: 74%

Section: Tlp Activation Of the Epithelial Sodium Channel (Enac)mentioning

confidence: 99%

See 1 more Smart Citation

Trypsin-Like Proteases and Their Role in Muco-Obstructive Lung Diseases

Carroll

Bailo

Reihill

et al. 2021

IJMS

View full text Add to dashboard Cite

Trypsin-like proteases (TLPs) belong to a family of serine enzymes with primary substrate specificities for the basic residues, lysine and arginine, in the P1 position. Whilst initially perceived as soluble enzymes that are extracellularly secreted, a number of novel TLPs that are anchored in the cell membrane have since been discovered. Muco-obstructive lung diseases (MucOLDs) are characterised by the accumulation of hyper-concentrated mucus in the small airways, leading to persistent inflammation, infection and dysregulated protease activity. Although neutrophilic serine proteases, particularly neutrophil elastase, have been implicated in the propagation of inflammation and local tissue destruction, it is likely that the serine TLPs also contribute to various disease-relevant processes given the roles that a number of these enzymes play in the activation of both the epithelial sodium channel (ENaC) and protease-activated receptor 2 (PAR2). More recently, significant attention has focused on the activation of viruses such as SARS-CoV-2 by host TLPs. The purpose of this review was to highlight key TLPs linked to the activation of ENaC and PAR2 and their association with airway dehydration and inflammatory signalling pathways, respectively. The role of TLPs in viral infectivity will also be discussed in the context of the inhibition of TLP activities and the potential of these proteases as therapeutic targets.

show abstract

Section: Over-activation Of Enac Leads To Airways Dehydration and Impaired Mucociliary Clearance Mechanisms In Mucoldsmentioning

confidence: 74%

Section: Tlp Activation Of the Epithelial Sodium Channel (Enac)mentioning

confidence: 99%