Mesenchymal maintenance of distal epithelial cell phenotype during late fetal lung development

2007 ◽  
Vol 292 (3) ◽  
pp. L725-L741 ◽  
Author(s):  
Julie Deimling ◽  
Kate Thompson ◽  
Irene Tseu ◽  
Jinxia Wang ◽  
Richard Keijzer ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Notch Pathway ◽  
Secretory Protein ◽  
Lung Epithelial Cells ◽  
Clara Cell ◽  
Cell Phenotype ◽  
Lung Epithelium ◽  
Morphological Pattern ◽  
Lung Epithelial ◽  
Distal Lung

Classical tissue recombination experiments have reported that at early gestation both tracheal and distal lung epithelium have the plasticity to respond to mesenchymal signals. Herein we examined the role of epithelial-mesenchymal interactions in maintaining epithelial differentiation at late (E19–E21, term = 22 days) fetal gestation in the rat. Isolated distal lung epithelial cells were recombined with mesenchymal cells from lung, skin, and intestine, and the homotypic or heterotypic recombinant cell aggregates were cultured for up to 5 days. Recombining lung epithelial cells with mesenchyme from various sources induced a morphological pattern that was specific to the type of inducing mesenchyme. In situ analysis of surfactant protein (SP)-C, SP-B, and Clara cell secretory protein (CCSP) expression, as well as SP-C and CCSP promoter transactivation experiments, revealed that distal lung epithelium requires lung mesenchyme to maintain the alveolar, but not bronchiolar, phenotype. Incubation of lung recombinants with an anti-FGF7 antibody resulted in a partial inhibition of mesenchyme-induced SP-C promoter transactivation. Immunoreactivity for Delta and Lunatic fringe, components of the Notch pathway that regulates cell differentiation, was downregulated in the heterotypic recombinants. In contrast, Hes1 mRNA expression was increased in these recombinants. Cumulatively, these results suggest that at late fetal gestation, distal lung epithelial cells are not fully committed to a specific phenotype and still have the plasticity to respond to various signals. Their alveolar phenotype is likely maintained by Notch/Notch ligand interactions and mesenchymal factors, including FGF7.

Inhibition of amiloride-sensitive sodium-channel activity in distal lung epithelial cells by nitric oxide

1998 ◽  
Vol 274 (3) ◽  
pp. L378-L387 ◽  
Author(s):  
Jin Wen Ding ◽  
John Dickie ◽  
Hugh O’Brodovich ◽  
Yutaka Shintani ◽  
Bijan Rafii ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Epithelial Cells ◽  
Cell Function ◽  
Short Circuit ◽  
Short Circuit Current ◽  
Lung Epithelial Cells ◽  
Flufenamic Acid ◽  
Activated Macrophages ◽  
Lung Epithelial ◽  
Distal Lung

Distal lung epithelial cells (DLECs) play an active role in fluid clearance from the alveolus by virtue of their ability to actively transport Na+ from the alveolus to the interstitial space. The present study evaluated the ability of activated macrophages to modulate the bioelectric properties of DLECs. Low numbers of lipopolysaccharide (LPS)-treated macrophages were able to significantly reduce amiloride-sensitive short-circuit current ( I sc) without affecting total I sc or monolayer resistance. This was associated with a rise in the flufenamic acid-sensitive component of the I sc. The effect was reversed by the addition of N-monomethyl-l-arginine to the medium, implying a role for nitric oxide. We hypothesized that macrophages exerted their effect by expressing inducible nitric oxide synthase (iNOS) in DLECs. The products of LPS-treated macrophages increased the levels of iNOS protein and mRNA transcripts in DLECs as well as causing a rise in iNOS activity. Immunofluorescence microscopy of LPS-stimulated macrophage-DLEC cocultures with anti-nitrotyrosine antibodies provided evidence for the generation of peroxynitrite in macrophages but not in DLECs. These data indicate that activated macrophages in the lung may contribute to impaired resolution of acute respiratory distress syndrome and suggest a novel mechanism whereby nitric oxide might alter cell function by altering its ion-transporting phenotype.

scholarly journals Mechanotransduction via TRPV4 regulates inflammation and differentiation in fetal mouse distal lung epithelial cells

2015 ◽  
Vol 16 (1) ◽  
Author(s):  
Pritha S. Nayak ◽  
Yulian Wang ◽  
Tanbir Najrana ◽  
Lauren M. Priolo ◽  
Mayra Rios ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Lung Epithelial Cells ◽  
Fetal Mouse ◽  
Lung Epithelial ◽  
Distal Lung

H2O2 mediates O2 toxicity in cultured fetal rat distal lung epithelial cells

1999 ◽  
Vol 26 (11-12) ◽  
pp. 1357-1368 ◽  
Author(s):  
Xiaoping Luo ◽  
Neil A Christie ◽  
Michael A McLaughlin ◽  
Rose Belcastro ◽  
Larisa Sedlackova ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Lung Epithelial Cells ◽  
Fetal Rat ◽  
Lung Epithelial ◽  
Distal Lung

Long-term terbutaline exposure stimulates α1-Na+-K+-ATPase expression at posttranscriptional level in rat fetal distal lung epithelial cells

2010 ◽  
Vol 298 (1) ◽  
pp. L96-L104 ◽  
Author(s):  
Muhammad S. Rahman ◽  
Shephali Gandhi ◽  
Gail Otulakowski ◽  
Wenming Duan ◽  
Aparna Sarangapani ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Atpase Activity ◽  
Apical Membrane ◽  
Short Circuit ◽  
Basolateral Membrane ◽  
Lung Epithelial Cells ◽  
Intracellular Camp ◽  
Adult Type ◽  
Lung Epithelial ◽  
Distal Lung

Transepithelial Na+ transport through epithelial Na+ channels (ENaC) on the apical membrane and Na+-K+-ATPase activity on the basolateral membrane of distal lung epithelial cells are critical for alveolar fluid clearance. Acute exposure to β-adrenergic agonists stimulates lung fluid clearance by increasing Na+ transport. We investigated the effects of chronic exposure to the β2-adrenergic agonist terbutaline on the transepithelial Na+ transport in rat fetal distal lung epithelia (FDLE). FDLE monolayers exposed to 10−4 M terbutaline for 48 h had significantly increased propanolol-blockable transepithelial total and amiloride-sensitive short-circuit current ( Isc); however, when these chronically exposed monolayers were acutely exposed to additional β-agonists and intracellular cAMP upregulators, there was no further increase in Isc. Monolayers exposed to terbutaline for >48 h had Isc similar to control cells. Ouabain-sensitive Na+-K+-ATPase activity was increased in 48-h terbutaline-exposed FDLE whose apical membranes were permeabilized with nystatin. In contrast, terbutaline did not increase amiloride-sensitive apical membrane Isc in FDLE whose basolateral membranes were permeabilized with nystatin. Terbutaline treatment did not affect α-, β-, or γ-ENaC mRNA or α-ENaC protein steady-state levels, but increased total cellular levels and rate of synthesis of α1-Na+-K+-ATPase protein in FDLE in the absence of any change in α1-Na+-K+-ATPase mRNA. Total cellular β1-Na+-K+-ATPase mRNA and protein levels were not affected by terbutaline. These data suggest that FDLE have different responses from adult type II epithelial cells when chronically exposed to terbutaline, and their increased transepithelial Na+ transport occurs via a posttranscriptional increase in α1-Na+-K+-ATPase expression.

scholarly journals Activation of the mTORC1/PGC-1 axis promotes mitochondrial biogenesis and induces cellular senescence in the lung epithelium

2019 ◽  
Vol 316 (6) ◽  
pp. L1049-L1060 ◽  
Author(s):  
Ross Summer ◽  
Hoora Shaghaghi ◽  
DeLeila Schriner ◽  
Willy Roque ◽  
Dominic Sales ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Cellular Senescence ◽  
Mitochondrial Biogenesis ◽  
Lung Epithelial Cells ◽  
Chronic Obstructive ◽  
Protective Mechanism ◽  
Peroxisome Proliferator ◽  
Lung Epithelium ◽  
Peroxisome Proliferator Activated Receptor ◽  
Lung Epithelial

Cellular senescence is a biological process by which cells lose their capacity to proliferate yet remain metabolically active. Although originally considered a protective mechanism to limit the formation of cancer, it is now appreciated that cellular senescence also contributes to the development of disease, including common respiratory ailments such as chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis. While many factors have been linked to the development of cellular senescence, mitochondrial dysfunction has emerged as an important causative factor. In this study, we uncovered that the mitochondrial biogenesis pathway driven by the mammalian target of rapamycin/peroxisome proliferator-activated receptor-γ complex 1α/β (mTOR/PGC-1α/β) axis is markedly upregulated in senescent lung epithelial cells. Using two different models, we show that activation of this pathway is associated with other features characteristic of enhanced mitochondrial biogenesis, including elevated number of mitochondrion per cell, increased oxidative phosphorylation, and augmented mitochondrial reactive oxygen species (ROS) production. Furthermore, we found that pharmacological inhibition of the mTORC1 complex with rapamycin not only restored mitochondrial homeostasis but also reduced cellular senescence to bleomycin in lung epithelial cells. Likewise, mitochondrial-specific antioxidant therapy also effectively inhibited mTORC1 activation in these cells while concomitantly reducing mitochondrial biogenesis and cellular senescence. In summary, this study provides a mechanistic link between mitochondrial biogenesis and cellular senescence in lung epithelium and suggests that strategies aimed at blocking the mTORC1/PGC-1α/β axis or reducing ROS-induced molecular damage could be effective in the treatment of senescence-associated lung diseases.

scholarly journals The effects of P O2 upon transepithelial ion transport in fetal rat distal lung epithelial cells

2000 ◽  
Vol 524 (2) ◽  
pp. 539-547 ◽  
Author(s):  
S. J. Ramminger ◽  
D. L. Baines ◽  
R. E. Olver ◽  
S. M. Wilson
Keyword(s):  
Epithelial Cells ◽  
Ion Transport ◽  
Lung Epithelial Cells ◽  
Fetal Rat ◽  
Lung Epithelial ◽  
Distal Lung

scholarly journals Fraction of MHCII and EpCAM expression characterizes distal lung epithelial cells for alveolar type 2 cell isolation

2017 ◽  
Vol 18 (1) ◽  
Author(s):  
Koichi Hasegawa ◽  
Atsuyasu Sato ◽  
Kazuya Tanimura ◽  
Kiyoshi Uemasu ◽  
Yoko Hamakawa ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Cell Isolation ◽  
Lung Epithelial Cells ◽  
Alveolar Type ◽  
Epcam Expression ◽  
Lung Epithelial ◽  
Distal Lung
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