High Concentrations of Plasminogen Activator Inhibitor-1 in Lungs of Preterm Infants With Respiratory Distress Syndrome

Cederqvist, Katariina; Sirén, Vappu; Petäjä, Jari; Vaheri, Antti; Haglund, Caj; Andersson, Sture

doi:10.1542/peds.2005-0870

Cited by 24 publications

(24 citation statements)

References 27 publications

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“…Hyperoxic injury up-regulates PAI-1 (34) in murine models and mice lacking the PAI-1 gene have a decreased fibrotic response to bleomycin (35). PAI-1 is elevated in preterm infants with respiratory distress syndrome (RDS) and may play a contributory role in bronchopulmonary dysplasia (36). The robust up-regulation of PAI-1 with transdifferentiation seen here supports the likely important role of PAI-1 in tissue repair in the alveolar microenvironment.…”

Section: Discussionsupporting

confidence: 55%

In Vitro Transdifferentiation of Human Fetal Type II Cells Toward a Type I–like Cell

et al. 2007

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For alveolar type I cells, phenotype plasticity and physiology other than gas exchange await further clarification due to in vitro study difficulties in isolating and maintaining type I cells in primary culture. Using an established in vitro model of human fetal type II cells, in which the type II phenotype is induced and maintained by adding hormones, we assessed for transdifferentiation in culture toward a type I-like cell with hormone removal for up to 144 h, followed by electron microscopy, permeability studies, and RNA and protein analysis. T he distal alveolar epithelium contains type I and II cells. Type II cells comprise 75% of distal lung epithelium, 7% of the surface area, and produce surfactant. Type II cells have many well-characterized markers, including lamellar bodies, surfactant proteins A, B, C, and D (SP-A, B, C, and D) (1), and the aspartic protease pepsinogen C (PGC) (2).Type I cells, although less numerous, cover 93% of adult lung surface area and provide the gas exchange surface (1). Other type I functions, such as ion transport and fluid homeostasis, are less known. Type I cells form a tight monolayer with low permeability (3). However, the utility of previously described type I biochemical markers (4) has been limited by variable reproducibility and expression between species.Challenges in isolation and culture have limited progress in type I cell biology. Despite isolated reports (5,6), there are no widespread primary culture models. Instead, rat type II cells transdifferentiated toward a type I cell on tissue culture plastic (7) have served as a proxy for type I cells (8,9). There are limited data with regards to transdifferentiation in adult human alveolar epithelium (10), with no previous in vivo descriptions in human fetal lung. Rodent model transdifferentiation and the observation that type II cells serve as progenitors of type I cells after alveolar injury in mature lung (11) have led to the assumption that type I cells are derived from type II cells. However, the possibility that both are derived from a common precursor and retain some degree of plasticity has not been examined in the human fetal lung.Because of its potential plasticity, fetal alveolar epithelium provides unique opportunities to study differentiation/ transdifferentiation pathway(s) in the developing lung. We previously demonstrated that type II cells from human fetal lung can maintain a differentiated phenotype with dexamethasone, cAMP, and isobutylmethylxanthine (DCI) (12) and that these conditions induce differentiation of type II cells from naive human fetal lung epithelium (13). Here, we demonstrate that DCI withdrawal from cultured human fetal type II cells results in transdifferentiation toward type I-like cells. Transdifferentiation is associated with diminution of type II morphology, decreased expression of type II markers, and induction of type I cell markers. Importantly, transdifferentiated cells behave like type I cells, with decreased permeability and increased transepithelial resistance (T...

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Section: Discussionsupporting

confidence: 55%

In Vitro Transdifferentiation of Human Fetal Type II Cells Toward a Type I–like Cell

et al. 2007

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“…Gene expression analysis of lung samples from short-term ventilated preterm infants was shown to have increased expression of THBS1 (31). Similarly increased levels of plasminogen activator inhibitor 1 (expressed by SERPINE1) in tracheal aspirate have been related to the severity of respiratory distress syndrome (32), and may be related to the development of BPD.…”

Section: Discussionmentioning

confidence: 98%

Age, Sexual Dimorphism, and Disease Associations in the Developing Human Fetal Lung Transcriptome

Kho

Chhabra

Sharma

et al. 2016

Am J Respir Cell Mol Biol

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The fetal origins of disease hypothesis suggests that variations in the course of prenatal lung development may affect life-long pulmonary function growth, decline, and pathobiology. Many studies support the existence of differences in the developing lung trajectory in males and females, and sex-specific differences in the prevalence of chronic lung diseases, such as asthma and bronchopulmonary dysplasia. The objectives of this study were to investigate the early developing fetal lung for transcriptomic correlates of postconception age (maturity) and sex, and their associations with chronic lung diseases. We analyzed whole-lung transcriptome profiles of 61 females and 78 males at 54-127 days postconception (dpc) from nonsmoking mothers using unsupervised principal component analysis and supervised linear regression models. We identified dominant transcriptomic correlates for postconception age and sex with corresponding gene sets that were enriched for developing lung structural and functional ontologies. We observed that the transcriptomic sex difference was not a uniform global time shift/lag, rather, lungs of males appear to be more mature than those of females before 96 dpc, and females appear to be more mature than males after 96 dpc. The age correlate gene set was consistently enriched for asthma and bronchopulmonary dysplasia genes, but the sex correlate gene sets were not. Despite sex differences in the developing fetal lung transcriptome, postconception age appears to be more dominant than sex in the effect of early fetal lung developments on disease risk during this early pseudoglandular phase of development.

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“…Hyperoxia has been reported to decrease uPA in airway epithelial cells and to increase PAI-1 in retinal pigment epithelial cells, effects that would diminish plasmin activity [41,42]. Indeed a recent report found increased PAI-1/ uPA ratios in premature infants with respiratory distress syndrome who were treated with O 2 [43]. Hence increases in secreted VEGF could be explained by a reduction in VEGF clearance.…”

Section: Discussionmentioning

confidence: 99%

Hyperoxia enhances VEGF release from A549 cells via post-transcriptional processes

Shenberger

Zhang

Powell

et al. 2007

Free Radical Biology and Medicine

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Exposure of animals to hyperoxia decreases lung VEGF mRNA expression concomitant with an acute increase in VEGF protein within the epithelial lining fluid (ELF). The VEGF concentration in ELF is in excess of that found in the plasma, leading to the hypothesis that hyperoxia stimulates the release of VEGF protein from stores within the extracellular matrix. To test this hypothesis in a cell culture system, we exposed A549 cells to 95% O 2 for 48 hrs followed by recovery in room air

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High Concentrations of Plasminogen Activator Inhibitor-1 in Lungs of Preterm Infants With Respiratory Distress Syndrome

Cited by 24 publications

References 27 publications

In Vitro Transdifferentiation of Human Fetal Type II Cells Toward a Type I–like Cell

In Vitro Transdifferentiation of Human Fetal Type II Cells Toward a Type I–like Cell

Age, Sexual Dimorphism, and Disease Associations in the Developing Human Fetal Lung Transcriptome

Hyperoxia enhances VEGF release from A549 cells via post-transcriptional processes

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