Pathogenic Mechanisms in Emphysema: From Protease Anti-Protease Imbalance to Apoptosis

Abboud, Raja T.

doi:10.5772/31744

Cited by 1 publication

(2 citation statements)

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“…Various types of lung disorders, such as the chronic obstructive lung disease, are known to be associated with protease/antiprotease imbalance (Abboud, 2012; Goopts et al, 2009). At present, the target proteases of Wfdc2 are unclear.…”

Section: Discussionmentioning

confidence: 99%

“…In addition to mucins and surfactants, the epithelial cells of the lung secrete numerous proteases and protease inhibitors – such as serine proteases, matrix metalloproteinases (MMPs), serine protease inhibitors and tissue inhibitor of metalloproteinases (TIMPs) – that together form the protease/protease-inhibitor web (Löffek et al, 2011; Abboud, 2012; Meyer and Jaspers, 2015). These proteases and protease inhibitors are deeply involved in the pathophysiology of neonatal respiratory distress syndrome (RDS) as well as other lung diseases such as emphysema, cystic fibrosis, infection and pulmonary fibrosis (Meyer and Jaspers, 2015; Taggart et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

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Lack of whey acidic protein four disulphide core (WFDC) 2 protease inhibitor causes neonatal death from respiratory failure in mice

Nakajima

Ono

Radović

et al. 2019

Disease Models &Amp; Mechanisms

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Respiratory failure is a life-threatening problem for pre-term and term infants, yet many causes remain unknown. Here, we present evidence that whey acidic protein (WAP) four-disulfide core domain protease inhibitor 2 (Wfdc2), a protease inhibitor previously unrecognized in respiratory disease, may be a causal factor in infant respiratory failure. Wfdc2 transcripts are detected in the embryonic lung and analysis of a Wfdc2-GFP knock-in mouse line shows that both basal and club cells, and type II alveolar epithelial cells (AECIIs), express Wfdc2 neonatally. Wfdc2-null-mutant mice display progressive atelectasis after birth with a lethal phenotype. Mutant lungs have multiple defects, including impaired cilia and the absence of mature club cells from the tracheo-bronchial airways, and malformed lamellar bodies in AECIIs. RNA sequencing shows significant activation of a pro-inflammatory pathway, but with low-quantity infiltration of mononuclear cells in the lung. These data demonstrate that Wfdc2 function is vitally important for lung aeration at birth and that gene deficiency likely causes failure of the lung mucosal barrier.

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Section: Discussionmentioning

confidence: 99%