scholarly journals Vascular Growth in the Fetal Lung

10.5772/26445 ◽  
2011 ◽  
Author(s):  
Stephen C.
Keyword(s):  
Fetal Lung ◽  
Vascular Growth

scholarly journals Control of HIF-1α and vascular signaling in fetal lung involves cross talk between mTORC1 and the FGF-10/FGFR2b/Spry2 airway branching periodicity clock

2010 ◽  
Vol 299 (4) ◽  
pp. L455-L471 ◽  
Author(s):  
C. L. Scott ◽  
D. J. Walker ◽  
E. Cwiklinski ◽  
C. Tait ◽  
A. R. Tee ◽  
...  
Keyword(s):  
Mammalian Target Of Rapamycin ◽  
Hypoxia Inducible Factor ◽  
Fetal Lung ◽  
Bronchial Epithelium ◽  
Vascular Bundles ◽  
Vascular Differentiation ◽  
Human Embryonic Lung ◽  
Vascular Growth ◽  
Mtorc1 Activation ◽  
Airway Branching

Lung development requires coordinated signaling between airway and vascular growth, but the link between these processes remains unclear. Mammalian target of rapamycin complex-1 (mTORC1) can amplify hypoxia-inducible factor-1α (HIF-1α) vasculogenic activity through an NH2-terminal mTOR binding (TOS) motif. We hypothesized that this mechanism coordinates vasculogenesis with the fibroblast growth factor (FGF)-10/FGF-receptor2b/Spry2 regulator of airway branching. First, we tested if the HIF-1α TOS motif participated in epithelial-mesenchymal vascular signaling. mTORC1 activation by insulin significantly amplified HIF-1α activity at fetal Po2 (23 mmHg) in human bronchial epithelium (16HBE14o-) and induced vascular traits (Flk1, sprouting) in cocultured human embryonic lung mesenchyme (HEL-12469). This enhanced activation of HIF-1α by mTORC1 was abolished on expression of a HIF-1α (F99A) TOS-mutant and also suppressed vascular differentiation of HEL-12469 cocultures. Next, we determined if vasculogenesis in fetal lung involved regulation of mTORC1 by the FGF-10/FGFR2b/Spry2 pathway. Fetal airway epithelium displayed distinct mTORC1 activity in situ, and its hyperactivation by TSC1−/− knockout induced widespread VEGF expression and disaggregation of Tie2-positive vascular bundles. FGF-10-coated beads grafted into fetal lung explants from Tie2-LacZ transgenic mice induced localized vascular differentiation in the peripheral mesenchyme. In rat fetal distal lung epithelial (FDLE) cells cultured at fetal Po2, FGF-10 induced mTORC1 and amplified HIF-1α activity and VEGF secretion without induction of ERK1/2. This was accompanied by the formation of a complex between Spry2, the cCBL ubiquitin ligase, and the mTOR repressor, TSC2, which abolished GTPase activity directed against Rheb, the G protein inducer of mTORC1. Thus, mTORC1 links HIF-1α-driven vasculogenesis with the FGF-10/FGFR2b/Spry2 airway branching periodicity regulator.

New Ultrastructural Observations on Injury and Regeneration of Cilia in Mammalian Conducting Airway Epithelium

1981 ◽  
Vol 39 ◽  
pp. 624-625
Author(s):  
J.L. Carson ◽  
A.M. Collier
Keyword(s):  
Respiratory Tract ◽  
Airway Epithelium ◽  
Defense Mechanisms ◽  
Normal Growth ◽  
Fetal Lung ◽  
Secretory Cells ◽  
Airway Epithelial ◽  
Ciliated Cells ◽  
Conducting Airway ◽  
Conducting Airways

The ciliated cells lining the conducting airways of mammals are integral to the defense mechanisms of the respiratory tract, functioning in coordination with secretory cells in the removal of inhaled and cellular debris. The effects of various infectious and toxic agents on the structure and function of airway epithelial cell cilia have been studied in our laboratory, both of which have been shown to affect ciliary ultrastructure.These observations have led to questions about ciliary regeneration as well as the possible induction of ciliogenesis in response to cellular injury. Classical models of ciliogenesis in the conducting airway epithelium of the mammalian respiratory tract have been based primarily on observations of the developing fetal lung. These observations provide a plausible explanation for the embryological generation of ciliary beds lining the conducting airways but do little to account for subsequent differentiation of ciliated cells and ciliogenesis during normal growth and development.

Collagen secretion mediated by NMDR activation in human fetal lung fibroblasts

2010 ◽  
Vol 34 (8) ◽  
pp. S70-S70
Author(s):  
MingJie WANG ◽  
ZiQiang LUO ◽  
Mei LU ◽  
LiHong SHANG ◽  
ShaoJie YUE
Keyword(s):  
Fetal Lung ◽  
Lung Fibroblasts ◽  
Collagen Secretion ◽  
Human Fetal Lung

Structure and Function of Angiopoietin-like Protein 3 (ANGPTL3) in Atherosclerosis

2020 ◽  
Vol 27 (31) ◽  
pp. 5159-5174 ◽  
Author(s):  
Xinjie Lu
Keyword(s):  
Low Density Lipoprotein ◽  
Lipoprotein Metabolism ◽  
Density Lipoprotein ◽  
Structure And Function ◽  
Biological Functions ◽  
Pharmacological Management ◽  
Vascular Growth ◽  
Promising Target ◽  
And Function ◽  
Systematic Appraisal

Background:Angiopoietin-Like Proteins (ANGPTLs) are structurally related to the angiopoietins. A total of eight ANGPTLs (from ANGPTL1 to ANGPTL8) have been identified so far. Most ANGPTLs possess multibiological functions on lipid metabolism, atherosclerosis, and cancer. Among them, ANGPTL3 has been shown to regulate the levels of Very Low-Density Lipoprotein (VLDL) made by the liver and play a crucial role in human lipoprotein metabolism.Method:A systematic appraisal of ANGPTLs was conducted, focusing on the main features of ANGPTL3 that has a significant role in atherosclerosis.Results:Angiopoietins including ANGPTL3 are vascular growth factors that are highly specific for endothelial cells, perform a variety of other regulatory activities to influence inflammation, and have been shown to possess both pro-atherosclerotic and atheroprotective effects.Conclusion:ANGPTL3 has been demonstrated as a promising target in the pharmacological management of atherosclerosis. However, many questions remain about its biological functions.

Effect of prenatal isoxsuprine on pulmonary oxygen toxicity in the newborn rat

1980 ◽  
Vol 48 (3) ◽  
pp. 505-510 ◽  
Author(s):  
L. Frank ◽  
J. Summerville ◽  
D. Massaro
Keyword(s):  
Enzyme Activities ◽  
Oxygen Toxicity ◽  
Fetal Lung ◽  
Antioxidant Enzyme Activities ◽  
Newborn Rats ◽  
Lung Maturation ◽  
Lung Weight ◽  
Pregnant Rats ◽  
Rat Pups ◽  
Hyperoxic Exposure

Isoxsuprine, a beta-sympathomimetic agent used clinically to delay premature parturition and to possibly accelerate fetal lung maturation, was administered to pregnant rats at 48 and 24 h prior to delivery. Newborn rats were placed in 96-98% O2 (or room air) to determine if the prenatal isoxsuprine treatment compromised their tolerance to prolonged hyperoxic exposure. (Exogenous catecholamines are known to exacerbate O2 toxicity in adult animals). Survival of the isoxsuprine-treated pups in O2 (52%) was no different than for control neonates exposed to hyperoxia for 7 days (57%) (P = 0.22). Body weight, lung weight, lung protein, and DNA content of the newborns were also not altered by the prenatal isoxsuprine treatment. Lung antioxidant enzyme activities for superoxide dismutase, catalase, and glutathione peroxidase were the same at birth in the isoxsuprine-treated and control rat pups, and the enzyme activities increased in response to hyperoxic exposure in each group to an equivalent degree. Thus, in utero treatment with isoxsuprine had no apparent adverse effect on newborn rats exposed to a prolonged O2 challenge.

scholarly journals Exosomes Derived From Senescent Cells Promote Cellular Senescence

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 132-133
Author(s):  
Genxiang Mao ◽  
Xiaogang Xu
Keyword(s):  
Current Knowledge ◽  
Fetal Lung ◽  
Notch Signaling Pathway ◽  
Cell Senescence ◽  
Control Group ◽  
Cell Cycle Distribution ◽  
Young Control ◽  
Intracellular Ros ◽  
Associated Proteins

Abstract Exosomes are one type of small-cell extracellular vesicles (sEVs), which together with the senescence-associated secretory phenotype (SASP) mainly constitute the senescent microenvironment and perform remotely intercellular communication. However, the effects of senescence on exosomes biosynthesis and secretion and its role in the cell senescence are still obscure. Here, we used human fetal lung diploid fibroblasts (2BS) passaged to PD50 to construct the senescent cells model in vitro, which were confirmed by senescence-related β-galactosidase staining, cell cycle distribution, and intracellular ROS levels. PD30 2BS was used as young control. We evaluated the exosomes derived from senescence and young control group respectively and investigated their regulation of senescence. We found that exosomes released from 2BS had typical sizes and cup-shapes morphology and their surface presented typical exosome-associated proteins. The number of exosomes secreted by senescent cells was significantly higher than that of young cells. Moreover, exosomal markers Alix, TSG101, and CD63 were all more expressed than young cells. Furthermore, we treat young cells with exosomes secreted by senescent cells, which can induce senescence-like changes in young cells, including increased SA-β-Gal activity, up-regulated p16 protein expression, and activation of the Notch signaling pathway. The above results imply that exosomes derived from senescent cells can promote cell senescence. The findings expand the current knowledge on exosomes-mediated aging and provide a novel understanding of the relationship between SASP and senescence. This study is supported by National Natural Science Foundation of China (No. 81771520 and 31702144).

scholarly journals Molecular regulation of lung maturation in near-term fetal sheep by maternal daily vitamin C treatment in late gestation

2021 ◽  
Author(s):  
Erin V. McGillick ◽  
Sandra Orgeig ◽  
Beth J. Allison ◽  
Kirsty L. Brain ◽  
Youguo Niu ◽  
...  
Keyword(s):  
Vitamin C ◽  
Lung Development ◽  
Fetal Lung ◽  
Late Gestation ◽  
Lung Maturation ◽  
Maternal Vitamin ◽  
Healthy Pregnancy ◽  
Daily Vitamin ◽  
Expression Of Genes ◽  
Fetal Lung Maturation

Abstract Background In the fetus, the appropriate balance of prooxidants and antioxidants is essential to negate the detrimental effects of oxidative stress on lung maturation. Antioxidants improve respiratory function in postnatal life and adulthood. However, the outcomes and biological mechanisms of antioxidant action in the fetal lung are unknown. Methods We investigated the effect of maternal daily vitamin C treatment (200 mg/kg, intravenously) for a month in late gestation (105–138 days gestation, term ~145 days) on molecular regulation of fetal lung maturation in sheep. Expression of genes and proteins regulating lung development was quantified in fetal lung tissue. The number of surfactant-producing cells was determined by immunohistochemistry. Results Maternal vitamin C treatment increased fetal lung gene expression of the antioxidant enzyme SOD-1, hypoxia signaling genes (HIF-2α, HIF-3α, ADM, and EGLN-3), genes regulating sodium movement (SCNN1-A, SCNN1-B, ATP1-A1, and ATP1-B1), surfactant maturation (SFTP-B and ABCA3), and airway remodeling (ELN). There was no effect of maternal vitamin C treatment on the expression of protein markers evaluated or on the number of surfactant protein-producing cells in fetal lung tissue. Conclusions Maternal vitamin C treatment in the last third of pregnancy in sheep acts at the molecular level to increase the expression of genes that are important for fetal lung maturation in a healthy pregnancy. Impact Maternal daily vitamin C treatment for a month in late gestation in sheep increases the expression of gene-regulating pathways that are essential for normal fetal lung development. Following late gestation vitamin C exposure in a healthy pregnancy, an increase in lung gene but not protein expression may act as a mechanism to aid in the preparation for exposure to the air-breathing environment after birth. In the future, the availability/development of compounds with greater antioxidant properties than vitamin C or more specific targets at the site of oxidative stress in vivo may translate clinically to improve respiratory outcomes in complicated pregnancies at birth.

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