scholarly journals Alveolar Type I Epithelial Cells: The Forgotten Cells in Fetal Lung Development and Lung Injury

2016 ◽  
Vol 2 (4) ◽  
pp. e6-e9 ◽  
Author(s):  
Tanbir Najrana ◽  
◽  
Juan Sanchez-Esteban ◽  
Keyword(s):  
Epithelial Cells ◽  
Lung Injury ◽  
Lung Development ◽  
Fetal Lung ◽  
Alveolar Type ◽  
Type I ◽  
Fetal Lung Development

scholarly journals A role for caveolin-1 in mechanotransduction of fetal type II epithelial cells

2010 ◽  
Vol 298 (6) ◽  
pp. L775-L783 ◽  
Author(s):  
Yulian Wang ◽  
Benjamin S. Maciejewski ◽  
Diana Drouillard ◽  
Melissa Santos ◽  
Michael A. Hokenson ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Epithelial Cells ◽  
Lung Development ◽  
Fetal Lung ◽  
Mechanical Stretch ◽  
Erk Pathway ◽  
Type Ii ◽  
Caveolin 1 ◽  
Fetal Lung Development ◽  
Type Ii Cell

Mechanical forces are critical for fetal lung development. Using surfactant protein C (SP-C) as a marker, we previously showed that stretch-induced fetal type II cell differentiation is mediated via the ERK pathway. Caveolin-1, a major component of the plasma membrane microdomains, is important as a signaling protein in blood vessels exposed to shear stress. Its potential role in mechanotransduction during fetal lung development is unknown. Caveolin-1 is a marker of type I epithelial cell phenotype. In this study, using immunocytochemistry, Western blotting, and immunogold electron microscopy, we first demonstrated the presence of caveolin-1 in embryonic day 19 (E19) rat fetal type II epithelial cells. By detergent-free purification of lipid raft-rich membrane fractions and fluorescence immunocytochemistry, we found that mechanical stretch translocates caveolin-1 from the plasma membrane to the cytoplasm. Disruption of the lipid rafts with cholesterol-chelating agents further increased stretch-induced ERK activation and SP-C gene expression compared with stretch samples without disruptors. Similar results were obtained when caveolin-1 gene was knocked down by small interference RNA. In contrast, adenovirus overexpression of the wild-type caveolin-1 or delivery of caveolin-1 scaffolding domain peptide inside the cells decreased stretch-induced ERK phosphorylation and SP-C mRNA expression. In conclusion, our data suggest that caveolin-1 is present in E19 fetal type II epithelial cells. Caveolin-1 is translocated from the plasma membrane to the cytoplasm by mechanical stretch and functions as an inhibitory protein in stretch-induced type II cell differentiation via the ERK pathway.

Effects of oligohydramnios on lung growth and maturation in the fetal rat

2002 ◽  
Vol 282 (3) ◽  
pp. L431-L439 ◽  
Author(s):  
Joseph A. Kitterman ◽  
Cheryl J. Chapin ◽  
Jeff N. Vanderbilt ◽  
Nicolas F. M. Porta ◽  
Louis M. Scavo ◽  
...  
Keyword(s):  
Fetal Lung ◽  
Alveolar Type ◽  
Type I ◽  
Type Ii Cells ◽  
Type Ii ◽  
Lung Growth ◽  
Type I Cells ◽  
Fetal Lung Development ◽  
Fetal Rat ◽  
I Cells

Oligohydramnios (OH) retards fetal lung growth by producing less lung distension than normal. To examine effects of decreased distension on fetal lung development, we produced OH in rats by puncture of uterus and fetal membranes at 16 days of gestation; fetuses were delivered at 21 or 22 days of gestation. Controls were position-matched littermates in the opposite uterine horn. OH lungs had lower weights and less DNA, protein, and water, but no differences in saturated phosphatidylcholine, surfactant proteins (SP)-A and -B, and mRNA for SP-A, -B, -C, and -D. To evaluate effects on epithelial differentiation, we used RTI40 and RTII70, proteins specific in lung to luminal surfaces of alveolar type I and II cells, respectively. At 22 days of gestation, OH lungs had less RTI40 mRNA ( P < 0.05) and protein ( P < 0.001), but RTII70 did not differ from controls. With OH, type I cells (in proportion to type II cells) covered less distal air space perimeter ( P < 0.01). We conclude that OH, which retards lung growth, has little effect on surfactant and impedes formation of type I cells relative to type II cells.

Ontogeny of type I procollagen expression during human fetal lung development

1995 ◽  
Vol 268 (2) ◽  
pp. L309-L320 ◽  
Author(s):  
R. M. Davila ◽  
D. deMello ◽  
E. C. Crouch
Keyword(s):  
Blood Vessels ◽  
Lung Development ◽  
Fetal Lung ◽  
Immunoperoxidase Staining ◽  
Type I ◽  
Collagen Deposition ◽  
Developmentally Regulated ◽  
Mrna Accumulation ◽  
Type I Procollagen ◽  
Fetal Lung Development

The cellular sites of type I procollagen (PCI) production were investigated during fetal and early postnatal human lung development. PCI-synthesizing cells and sites of recent collagen deposition were visualized by immunoperoxidase staining of lung tissue with monoclonal antibodies to human PCI. In selected cases, serial sections were also examined by in situ hybridization to establish the cellular sites of PCI gene expression and mRNA accumulation. PCI cytoplasmic immunostaining generally correlated with sites of mRNA accumulation and with known sites of interstitial collagen deposition, including the adventitial and muscular layers of large blood vessels, submesothelial and peribronchial connective tissue, perichondrium, and interstitial matrix. However, we also observed developmental changes in relative PCI expression for each of these compartments, heterogeneity in the level of PCI expression by cells within individual anatomic subcompartments, and variations in the level of PCI expression along the length of pulmonary blood vessels and airways. These studies emphasize the complexity of developmentally regulated alterations in procollagen production during lung development.

Matrix metalloproteinases and tissue inhibitor of metalloproteinase-2 in fetal rabbit lung

2000 ◽  
Vol 279 (3) ◽  
pp. L555-L561 ◽  
Author(s):  
Yuh Fukuda ◽  
Masamichi Ishizaki ◽  
Yasunori Okada ◽  
Motoharu Seiki ◽  
Nobuaki Yamanaka
Keyword(s):  
Extracellular Matrix ◽  
Epithelial Cells ◽  
Matrix Metalloproteinases ◽  
Late Stage ◽  
Lung Development ◽  
Gelatin Zymography ◽  
Fetal Lung ◽  
Tissue Inhibitor Of Metalloproteinase ◽  
Fetal Lung Development ◽  
Tissue Homogenates

Cell-extracellular matrix interaction and extracellular matrix remodeling are known to be important in fetal lung development. We investigated the localization of matrix metalloproteinases (MMPs) in fetal rabbit lungs. Immunohistochemistry for type IV collagen, MMP-1, MMP-2, MMP-9, membrane type (MT) 1 MMP, and tissue inhibitor of metalloproteinase (TIMP)-2 and in situ hybridization for MMP-9 mRNA were performed. Gelatin zymography and Western blotting for MT1-MMP in lung tissue homogenates were also studied. MMP-1 and MT1-MMP were detected in epithelial cells, and MMP-2 and TIMP-2 were detected in epithelial cells and some mesenchymal cells in each stage. MMP-9 was found in epithelial cells mainly in the late stage. Gelatin zymography revealed that the ratio of active MMP-2 to latent MMP-2 increased dramatically during the course of development. MT1-MMP was detected in tissue homogenates, especially predominant in the late stage. These findings suggest that MMPs and their inhibitors may contribute to the formation of airways and alveoli in fetal lung development and that activated MMP-2 of alveolar epithelial cells may function to provide an extremely wide alveolar surface.

Mesenchymal determination of mechanical strain-induced fetal lung cell proliferation

1998 ◽  
Vol 275 (3) ◽  
pp. L545-L550 ◽  
Author(s):  
Jing Xu ◽  
Mingyao Liu ◽  
A. Keith Tanswell ◽  
Martin Post
Keyword(s):  
Epithelial Cells ◽  
Dna Synthesis ◽  
Lung Development ◽  
Mechanical Strain ◽  
Fetal Lung ◽  
Cell Types ◽  
Fetal Lung Development ◽  
Fetal Rat ◽  
Fetal Rat Lung ◽  
Fetal Breathing Movements

Fetal breathing movements play an important role in normal fetal lung growth. We have previously shown that an intermittent mechanical strain regimen (60 cycles/min, 15 min/h), simulating normal fetal breathing movements, stimulated growth of mixed fetal rat lung cells in organotypic culture. In the present study, we examined the individual responses of the two major fetal lung cell types, fibroblasts and epithelial cells, to mechanical strain. Also, we investigated the effect of mesenchymal-epithelial interactions on strain-induced cell proliferation during fetal lung development. Fibroblasts and epithelial cells from day 18to day 21 fetal rat lung (term = 22 days), cultured alone or as various recombinants, were subjected to either a 48-h static culture or to strain, and DNA synthesis was measured. Both cell types responded individually to strain with enhanced DNA synthesis throughout late fetal lung development. Independent of the recombination ratio, there was no additive response to strain when fibroblasts and epithelial cells from the same gestation were recombined. In contrast, strain-induced DNA synthesis was suppressed when cells from different gestations were recombined. The ontogenic response pattern of recombinants to mechanical strain was similar to that of fibroblasts but not of epithelial cells. Strain-induced proliferation increased and peaked at the early canalicular stage of lung development at 19 days of gestation and declined thereafter. We conclude that strain-enhanced growth of the fetal lung is gestation dependent and that the gestational response to mechanical force is regulated by the mesenchyme.

scholarly journals EphB6 Regulates TFEB-Lysosomal Pathway and Survival of Disseminated Indolent Breast Cancer Cells

Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1079
Author(s):  
Manuela Zangrossi ◽  
Patrizia Romani ◽  
Probir Chakravarty ◽  
Colin D.H. Ratcliffe ◽  
Steven Hooper ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Epithelial Cells ◽  
Cancer Cells ◽  
Lung Epithelial Cells ◽  
Late Relapse ◽  
Alveolar Type ◽  
Type I ◽  
Extrinsic Factors ◽  
Lung Epithelial

Late relapse of disseminated cancer cells is a common feature of breast and prostate tumors. Several intrinsic and extrinsic factors have been shown to affect quiescence and reawakening of disseminated dormant cancer cells (DDCCs); however, the signals and processes sustaining the survival of DDCCs in a foreign environment are still poorly understood. We have recently shown that crosstalk with lung epithelial cells promotes survival of DDCCs of estrogen receptor-positive (ER+) breast tumors. By using a lung organotypic system and in vivo dissemination assays, here we show that the TFEB-lysosomal axis is activated in DDCCs and that it is modulated by the pro-survival ephrin receptor EphB6. TFEB lysosomal direct targets are enriched in DDCCs in vivo and correlate with relapse in ER+ breast cancer patients. Direct coculture of DDCCs with alveolar type I-like lung epithelial cells and dissemination in the lung drive lysosomal accumulation and EphB6 induction. EphB6 contributes to survival, TFEB transcriptional activity, and lysosome formation in DDCCs in vitro and in vivo. Furthermore, signaling from EphB6 promotes the proliferation of surrounding lung parenchymal cells in vivo. Our data provide evidence that EphB6 is a key factor in the crosstalk between disseminated dormant cancer cells and the lung parenchyma and that the TFEB-lysosomal pathway plays an important role in the persistence of DDCCs.

Fetal lung development via quantitative biomarkers from diffusion MRI and histological validation in rhesus macaques

2021 ◽  
Author(s):  
Nara S. Higano ◽  
Xuefeng Cao ◽  
Jinbang Guo ◽  
Xiaojie Wang ◽  
Christopher D. Kroenke ◽  
...  
Keyword(s):  
Lung Development ◽  
Diffusion Mri ◽  
Rhesus Macaques ◽  
Fetal Lung ◽  
Fetal Lung Development ◽  
Histological Validation

scholarly journals Receptor for advanced glycation end-products (RAGE) is an indicator of direct lung injury in models of experimental lung injury

2009 ◽  
Vol 297 (1) ◽  
pp. L1-L5 ◽  
Author(s):  
Xiao Su ◽  
Mark R. Looney ◽  
Naveen Gupta ◽  
Michael A. Matthay
Keyword(s):  
Lung Injury ◽  
Advanced Glycation End Products ◽  
Cell Injury ◽  
Alveolar Epithelial Cell ◽  
Experimental Models ◽  
Alveolar Type ◽  
Type I ◽  
Advanced Glycation ◽  
Glycation End Products ◽  
End Products

Receptor for advanced glycation end-products (RAGE) is a marker of alveolar type I cells and is elevated in the pulmonary edema fluid of patients with acute lung injury (ALI). We tested the hypothesis that RAGE in the bronchoalveolar lavage (BAL) would be elevated in experimental models of direct ALI characterized by alveolar epithelial cell injury. We developed ELISA measurements for RAGE and studied ALI (direct and indirect) mouse models and collected BAL at specified endpoints to measure RAGE. We also tested whether levels of BAL RAGE correlated 1) with the severity of lung injury in acid and hyperoxia-induced ALI and 2) with the beneficial effect of a novel treatment, mesenchymal stem cells (MSC), in LPS-induced ALI. In ALI models of direct lung injury induced by intratracheal instillation of acid, LPS, or Escherichia coli, the BAL RAGE was 58-, 22-, and 13-fold elevated, respectively. In contrast, BAL RAGE was not detectable in indirect models of ALI induced by an intraperitoneal injection of thiourea or by an intravenous injection of MHC I monoclonal antibody that produces a mouse model of transfusion-related ALI. BAL RAGE did correlate with the severity of lung injury in acid and hyperoxia-induced ALI. In addition, with LPS-induced ALI, BAL RAGE was markedly reduced with MSC treatment. In summary, BAL RAGE is an indicator of ALI, and it may be useful in distinguishing direct from indirect models of ALI as well as assessing the response to specific therapies.

scholarly journals In utero administration of GABA promotes fetal lung development

2010 ◽  
Vol 24 (S1) ◽  
Author(s):  
Narendranath Reddy Chintagari ◽  
Yang Wang ◽  
Dong Xi ◽  
Lin Liu
Keyword(s):  
Lung Development ◽  
Fetal Lung ◽  
In Utero ◽  
Fetal Lung Development
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