The effect of mechanical strain on fetal rat lung cell proliferation: Comparison of two-and three-dimensional culture systems

1995 ◽  
Vol 31 (11) ◽  
pp. 858-866 ◽  
Author(s):  
Mingyao Liu ◽  
Jing Xu ◽  
Patricia Souza ◽  
Bryony Tanswell ◽  
A. Keith Tanswell ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Mechanical Strain ◽  
Three Dimensional ◽  
Rat Lung ◽  
Culture Systems ◽  
Fetal Rat ◽  
Fetal Rat Lung ◽  
Three Dimensional Culture

Inhibition of mechanical strain-induced fetal rat lung cell proliferation by gadolinium, a stretch-activated channel blocker

1994 ◽  
Vol 161 (3) ◽  
pp. 501-507 ◽  
Author(s):  
Mingyao Liu ◽  
Jing Xu ◽  
A. Keith Tanswell ◽  
Martin Post
Keyword(s):  
Cell Proliferation ◽  
Channel Blocker ◽  
Mechanical Strain ◽  
Rat Lung ◽  
Fetal Rat ◽  
Fetal Rat Lung

scholarly journals Mechanical strain-induced posttranscriptional regulation of fibronectin production in fetal lung cells

1999 ◽  
Vol 277 (1) ◽  
pp. L142-L149 ◽  
Author(s):  
Eric Mourgeon ◽  
Jing Xu ◽  
A. Keith Tanswell ◽  
Mingyao Liu ◽  
Martin Post
Keyword(s):  
Cell Proliferation ◽  
Mechanical Strain ◽  
Fetal Lung ◽  
Northern Analysis ◽  
Normal Lung ◽  
Lung Cells ◽  
Mrna Levels ◽  
Rat Lung ◽  
Fetal Rat ◽  
Fetal Rat Lung

We have shown that intermittent mechanical strain, simulating fetal breathing movements, stimulated fetal rat lung cell proliferation. Because normal lung growth requires proper coordination between cell proliferation and extracellular matrix remodeling, we investigated the effect of strain on fibronectin metabolism. Organotypic cultures of fetal rat lung cells, subjected to intermittent strain, showed increased fibronectin content in the culture media. Fibronectin-degrading activity in media from strained cells was similar to that of static cultures. Northern analysis revealed that strain inhibited fibronectin mRNA accumulation seen during static culture. Synthesis of fibronectin, determined by metabolic labeling, was increased by strain despite lower mRNA levels or presence of actinomycin D. This increase was not mediated via a rapamycin-sensitive mechanism. Strain stimulated prelabeled fibronectin secretion even in the presence of cycloheximide. These results suggest that strain differentially regulates fibronectin production of fetal lung cells at the transcriptional and posttranscriptional levels. Mechanical strain increases soluble fibronectin content by stimulating its synthesis and secretion without increasing fibronectin message levels.

Differential regulation of extracellular matrix molecules by mechanical strain of fetal lung cells

1999 ◽  
Vol 276 (5) ◽  
pp. L728-L735 ◽  
Author(s):  
Jing Xu ◽  
Mingyao Liu ◽  
Martin Post
Keyword(s):  
Extracellular Matrix ◽  
Cell Proliferation ◽  
Mechanical Strain ◽  
Fetal Lung ◽  
Lung Cells ◽  
Gelatinase A ◽  
Rat Lung ◽  
Fetal Rat ◽  
Gene And Protein Expression ◽  
Fetal Rat Lung

We have previously shown that an intermittent mechanical strain regimen (5% elongation, 60 cycles/min, 15 min/h) that simulates fetal breathing movements stimulated fetal rat lung cell proliferation. Because normal lung growth requires proper coordination between cell proliferation and extracellular matrix (ECM) remodeling, we subjected organotypic cultures of fetal rat lung cells ( day 19 of gestation, term = 22 days) to this strain regimen and examined alterations in ECM gene and protein expression. Northern analysis revealed that mechanical strain reduced messages for procollagen-α1(I) and biglycan and increased the levels of mRNA for collagen-α1(IV) and -α2(IV), whereas laminin β-chain mRNA levels remained constant. Regardless of mRNA changes, mechanical strain increased the protein content of type I and type IV collagen as well as of biglycan in the medium. Mechanical strain did not affect gene expression of several matrix metalloproteinases (MMPs), such as MMP-1 (interstitial collagenase), MMP-2 (gelatinase A), and MMP-3 (stromelysin-1). Neither collagenase nor gelatinase (A and B) activities in conditioned medium were affected by mechanical strain. Tissue inhibitor of metalloproteinase activities in conditioned medium remained unchanged during the 48-h intermittent mechanical stretching. These data suggest that an intermittent mechanical strain differentially regulates gene and protein expression of ECM molecules in fetal lung cells. The observed increase in matrix accumulation appears to be mainly a result of an increased synthesis of ECM molecules and not of decreasing activity of degradative enzymes.

Mechanical strain-enhanced fetal lung cell proliferation is mediated by phospholipase C and D and protein kinase C

1995 ◽  
Vol 268 (5) ◽  
pp. L729-L738 ◽  
Author(s):  
M. Liu ◽  
J. Xu ◽  
J. Liu ◽  
M. E. Kraw ◽  
A. K. Tanswell ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Phospholipase C ◽  
Second Messengers ◽  
Mechanical Strain ◽  
Rat Lung ◽  
Dependent Protein Kinase ◽  
Fetal Rat ◽  
Fetal Rat Lung ◽  
Dependent Protein ◽  
Pkc Activation

The signaling pathways by which intermittent strain (60 cycles/min, 15 min/h) regulates proliferation of mixed fetal rat lung cell in vitro have been investigated. Adenosine 3',5'-cyclic monophosphate (cAMP) content and cAMP-dependent protein kinase (PKA) activity were not affected by strain. The stimulatory effect of strain on DNA synthesis was also not influenced by the cyclic nucleotide-dependent protein kinase inhibitors H-8 or HA-1004, the adenylate cyclase inhibitor SQ-22536, or a PKA inhibitor and cAMP antagonist, adenosine 3',5'-cyclic monophosphothioate (Rp-cAMPS). In contrast, intracellular concentrations of two second messengers, inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG), were dramatically increased after a short period of strain. This increase in second messengers was accompanied by an increased tyrosine phosphorylation of phospholipase C-gamma 1. Phospholipase D activity was also increased by strain. Mechanical strain elicited a shift in the subcellular distribution of PKC activity from cytosol to membranes shortly after the onset of strain. The specific activity of PKC in the membranes increased 6- to 10-fold within 5-15 min and remained increased throughout a 48-h period of intermittent strain. Strain-induced PKC activation and DNA synthesis were blocked by the PKC inhibitors H-7, staurosporine, and calphostin C, as well as by the phospholipase C inhibitor U-73,122. We conclude that mechanical strain of mixed fetal rat lung cells activates phospholipid turnover via phospholipases, followed by PKC activation, which then triggers the downstream events that lead to cell proliferation.

The formation of histotypic structures from monodisperse fetal rat lung cells cultured on a three-dimensional substrate

In Vitro ◽  
1976 ◽  
Vol 12 (5) ◽  
pp. 373-381 ◽  
Author(s):  
William H. J. Douglas ◽  
Gary W. Moorman ◽  
Robert W. Teel
Keyword(s):  
Three Dimensional ◽  
Lung Cells ◽  
Rat Lung ◽  
Fetal Rat ◽  
Fetal Rat Lung ◽  
Cells Cultured

Identification of Betamethasone-Regulated Target Genes and Cell Pathways in Fetal Rat Lung Mesenchymal Fibroblasts

Endocrinology ◽  
2019 ◽  
Vol 160 (8) ◽  
pp. 1868-1884 ◽  
Author(s):  
Bennet K L Seow ◽  
Annie R A McDougall ◽  
Kelly L Short ◽  
Megan J Wallace ◽  
Stuart B Hooper ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Preterm Birth ◽  
Transcriptome Sequencing ◽  
Target Genes ◽  
Fetal Lung ◽  
Lung Fibroblasts ◽  
Matrix Remodeling ◽  
Rat Lung ◽  
Fetal Rat ◽  
Fetal Rat Lung

Abstract Preterm birth is characterized by severe lung immaturity that is frequently treated antenatally or postnatally with the synthetic steroid betamethasone. The underlying cellular targets and pathways stimulated by betamethasone in the fetal lung are poorly defined. In this study, betamethasone was compared with corticosterone in steroid-treated primary cultures of fetal rat lung fibroblasts stimulated for 6 hours and analyzed by whole-cell transcriptome sequencing and glucocorticoid (GC) receptor (GR) chromatin immunoprecipitation sequencing (ChIP-Seq) analysis. Strikingly, betamethasone stimulated a much stronger transcriptional response compared with corticosterone for both induced and repressed genes. A total of 483 genes were significantly stimulated by betamethasone or corticosterone, with 476 stimulated by both steroids, indicating a strong overlap in regulation. Changes in mRNA levels were confirmed by quantitative PCR for eight induced and repressed target genes. Pathway analysis identified cell proliferation and cytoskeletal/cell matrix remodeling pathways as key processes regulated by both steroids. One target, transglutaminase 2 (Tgm2), was localized to fetal lung mesenchymal cells. Tgm2 mRNA and protein levels were strongly increased in fibroblasts by both steroids. Whole-genome GR ChIP-Seq analysis with betamethasone identified GC response element–binding sites close to the previously characterized GR target genes Per1, Dusp1, Fkbp5, and Sgk1 and near the genes identified by transcriptome sequencing encoding Crispld2, Tgm2, Hif3α, and Kdr, defining direct genomic induction of expression in fetal lung fibroblasts via the GR. These results demonstrate that betamethasone stimulates specific genes and cellular pathways controlling cell proliferation and extracellular matrix remodeling in lung mesenchymal fibroblasts, providing a basis for betamethasone’s treatment efficacy in preterm birth.

scholarly journals Mechanical Strain Induces pp60 Activation and Translocation to Cytoskeleton in Fetal Rat Lung Cells

1996 ◽  
Vol 271 (12) ◽  
pp. 7066-7071 ◽  
Author(s):  
Mingyao Liu ◽  
Yi Qin ◽  
Jason Liu ◽  
A. Keith Tanswell ◽  
Martin Post
Keyword(s):  
Mechanical Strain ◽  
Lung Cells ◽  
Rat Lung ◽  
Fetal Rat ◽  
Fetal Rat Lung

Spatial and temporal differences in fibroblast behavior in fetal rat lung

1991 ◽  
Vol 261 (6) ◽  
pp. L424-L433 ◽  
Author(s):  
I. Caniggia ◽  
I. Tseu ◽  
R. N. Han ◽  
B. T. Smith ◽  
K. Tanswell ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Growth Factor ◽  
Epithelial Cell ◽  
Lung Development ◽  
Epithelial Cell Proliferation ◽  
Rat Lung ◽  
Fetal Rat ◽  
Fetal Rat Lung ◽  
Growth Promoting ◽  
In Cells

Fibroblast-epithelial interactions were investigated in cells from late-gestation fetal rat lung. Fibroblasts from the pseudoglandular stage of lung development stimulated epithelial cell proliferation, whereas fibroblasts from the saccular stage promoted epithelial cell differentiation. The developmental switch from proliferation to differentiation seemed to be controlled by both cell types. Fibroblast-derived epithelial cell growth-promoting activity, evident in cells from the pseudoglandular period, decreased during development and almost disappeared in cells from the saccular stage. Interestingly, the response of epithelial cells to this growth-promoting activity declined with advancing gestational age as epithelial cells became more responsive to fibroblast-derived differentiation factor(s). Production of differentiation factor(s) by fibroblasts increased during the canalicular stage of lung development. Platelet-derived growth factor (PDGF) and low concentrations of transforming growth factor-beta (TGF-beta) stimulated epithelial cell proliferation. PDGF did not affect differentiation, whereas TGF-beta was inhibitory. Dependent on their proximity to the epithelium, two subpopulations of fibroblasts that differed in their ability to promote epithelial cell proliferation or differentiation were isolated. Fibroblasts in close proximity to the epithelium mainly produced differentiation factors, whereas more distant fibroblasts primarily stimulated proliferation.

Maturation of fetal rat lung in diabetic pregnancies of graduated severity

Diabetes ◽  
1985 ◽  
Vol 34 (8) ◽  
pp. 734-743 ◽  
Author(s):  
J. R. Bourbon ◽  
B. Pignol ◽  
L. Marin ◽  
M. Rieutort ◽  
C. Tordet
Keyword(s):  
Rat Lung ◽  
Fetal Rat ◽  
Fetal Rat Lung
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