Unimpaired postnatal respiratory adaptation in a preterm human infant with a homozygous ENaC-α unit loss-of-function mutation

Huppmann, Stephanie; Lankes, Erwin; Schnabel, Dirk; Bührer, Christoph

doi:10.1038/jp.2011.46

Cited by 12 publications

(6 citation statements)

References 15 publications

(16 reference statements)

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“…residue is located in the transmembrane segment, similar to the A63 residue. Huppmann et al30 reported a Tunisian patient with sysPHA1, similar to our patient 6. Patients 7 and 8 are cousins and were found to have the homozygous p.527delF in SCNN1A.…”

supporting

confidence: 89%

Molecular genetic studies in a case series of isolated hypoaldosteronism due to biosynthesis defects or aldosterone resistance

Turan

Kotan

Taştan

et al. 2018

Clinical Endocrinology

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supporting

confidence: 89%

Molecular genetic studies in a case series of isolated hypoaldosteronism due to biosynthesis defects or aldosterone resistance

Turan

Kotan

Taştan

et al. 2018

Clinical Endocrinology

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“…Knockout of the a subunit in mice resulted in persistent lung fluid at birth and death from respiratory failure (24). Interestingly, a case report described a homozygous ENaC-a preterm infant who did not suffer any evidence of respiratory failure (25). Thus, in contrast to mice, clearance of alveolar fluid after birth in humans may not critically depend on ENaC.…”

Section: In Vitro and In Situ Studiesmentioning

confidence: 99%

Resolution of Pulmonary Edema. Thirty Years of Progress

Matthay

2014

Am J Respir Crit Care Med

136

111

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In the last 30 years, we have learned much about the molecular, cellular, and physiological mechanisms that regulate the resolution of pulmonary edema in both the normal and the injured lung. Although the physiological mechanisms responsible for the formation of pulmonary edema were identified by 1980, the mechanisms that explain the resolution of pulmonary edema were not well understood at that time. However, in the 1980s several investigators provided novel evidence that the primary mechanism for removal of alveolar edema fluid depended on active ion transport across the alveolar epithelium. Sodium enters through apical channels, primarily the epithelial sodium channel, and is pumped into the lung interstitium by basolaterally located Na/K-ATPase, thus creating a local osmotic gradient to reabsorb the water fraction of the edema fluid from the airspaces of the lungs. The resolution of alveolar edema across the normally tight epithelial barrier can be up-regulated by cyclic adenosine monophosphate (cAMP)-dependent mechanisms through adrenergic or dopamine receptor stimulation, and by several cAMPindependent mechanisms, including glucocorticoids, thyroid hormone, dopamine, and growth factors. Whereas resolution of alveolar edema in cardiogenic pulmonary edema can be rapid, the rate of edema resolution in most patients with acute respiratory distress syndrome (ARDS) is markedly impaired, a finding that correlates with higher mortality. Several mechanisms impair the resolution of alveolar edema in ARDS, including cell injury from unfavorable ventilator strategies or pathogens, hypoxia, cytokines, and oxidative stress. In patients with severe ARDS, alveolar epithelial cell death is a major mechanism that prevents the resolution of lung edema.Keywords: acute respiratory distress syndrome; acute lung injury; alveolar epithelium; alveolar liquid clearance; pulmonary edemaThe physiological basis for the formation of pulmonary edema was established by 1980. Cardiogenic pulmonary edema develops because of elevated vascular pressures in the lung (1), hence the term hydrostatic lung edema. Noncardiogenic pulmonary edema, clinically recognized as the acute respiratory distress syndrome (ARDS), is primarily the consequence of an increase in lung vascular and epithelial permeability (2). Several experimental studies had reported that the combination of elevated vascular pressure and an increase in lung vascular permeability would increase the accumulation of pulmonary edema (3, 4). And, in fact, elevated lung vascular pressures do coexist with an increase in lung vascular permeability in some clinical conditions that lead to ARDS, including sepsis and major trauma, as demonstrated definitively in a National Heart, Lung, and Blood Institute-supported multicenter clinical trial (5).However, the mechanisms responsible for the resolution of pulmonary edema were not well understood until research in the 1980s identified the primary mechanism responsible for the resolution of alveolar edema-active ion transport across the a...

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“…Much evidence confirmed that Na + absorption is an important means to maintain ASL homeostasis, and ENaC play a key role in Na + absorption (Tarran et al, 2001; Ji et al, 2012). Studies have shown that ENaC play a major role in respiratory diseases (Huppmann et al, 2011; Almaca et al, 2013), thus we explored the effects of influenza virus on ENaC.…”

Section: Discussionmentioning

confidence: 99%

Upregulation of the WNK4 Signaling Pathway Inhibits Epithelial Sodium Channels of Mouse Tracheal Epithelial Cells After Influenza A Infection

et al. 2019

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Influenza virus has a significant impact on the respiratory system. The mechanism of how influenza virus impairs the fluid transport in airway is not fully understood. We examined its effects on epithelial sodium channels (ENaC), which are very important for water and salt transport in the respiratory system. We focused on the impacts of influenza virus on ENaC activity in mouse tracheal epithelial cells (MTECs) and applied Ussing chamber apparatus for recording the short-circuit currents in primary cultured MTECs. Expressions of α and γ-ENaC were measured at the protein and mRNA levels by western blot and quantitative real-time polymerase chain reaction, respectively. Roles of the with-no-lysine-kinase-4 (WNK4) pathway were considered in participating influenza virus-involved ENaC regulation by using siRNA to knockdown WNK4 and the physical properties of airway surface liquid (ASL) were detected by confocal microscopy. Our results showed that influenza virus reduced ENaC activity, and the expressions of α and γ-ENaC were decreased at the protein and mRNA levels, respectively. WNK4 expression increased time-dependently at the protein level after influenza virus infection, while knockdown of WNK4 rescued the impact of influenza virus on ENaC and ASL height increased obviously after MTECs were treated with influenza virus. Taken together, these results suggest that influenza virus causes the changes of biophysical profile in the airway by altering the ENaC activity at least partly via facilitating the expression of WNK4.

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Unimpaired postnatal respiratory adaptation in a preterm human infant with a homozygous ENaC-α unit loss-of-function mutation

Cited by 12 publications

References 15 publications

Molecular genetic studies in a case series of isolated hypoaldosteronism due to biosynthesis defects or aldosterone resistance

Molecular genetic studies in a case series of isolated hypoaldosteronism due to biosynthesis defects or aldosterone resistance

Resolution of Pulmonary Edema. Thirty Years of Progress

Upregulation of the WNK4 Signaling Pathway Inhibits Epithelial Sodium Channels of Mouse Tracheal Epithelial Cells After Influenza A Infection

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