Endothelial-monocyte activating polypeptide II disrupts alveolar epithelial type II to type I cell transdifferentiation

Chen, Yao; Legan, Susan K.; Mahan, Anne; Thornton, Janet; Xu, Haiming; Schwarz, Margaret A.

doi:10.1186/1465-9921-13-1

Cited by 45 publications

(35 citation statements)

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“…Epidemiological data indicate these two conditions are linked; obese individuals are at greater risk for asthma development, increased severity, symptoms, treatment resistance and reduced quality of life (QOL) than non-obese individuals (2–4). Nearly 20% of obese adolescents have asthma, compared to 14.2% of non-obese adolescents (5).…”

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confidence: 99%

Relationships among obesity, physical activity and sedentary behavior in young adolescents with and without lifetime asthma

2015

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Objective To examine the interrelationships among body mass index (BMI), physical activity, sedentary behavior and gender in urban, low-income, primarily African American young adolescents with or without lifetime asthma. Methods Data were collected in 2002–2004 from 626 12-year old adolescents who were children of women who participated in the New Mother’s Study in Memphis, TN (1990 – 91). Adolescents with and without asthma were compared on BMI, physical activity and sedentary behavior. Multiple linear regression models were used to examine the association of asthma, gender and BMI with physical activity and sedentary behavior. Results Complete data were available for 545 adolescents. 11% of adolescents had lifetime asthma. Asthma and gender were associated with high-intensity physical activity (p < .001). Adolescents with asthma participated in less physical activity and girls participated less than boys. Gender was associated with sedentary behavior (p < .001): boys used personal computer (pc)/video after school more than girls. Girls with asthma had a higher BMI than girls without asthma (p = .027). Boys with asthma were less physically active than boys without asthma (p < .05). Conclusions Adolescents with asthma are less physically active than those without asthma and girls are less active than boys. Clinicians who provide care for adolescents with asthma are encouraged to assess physical activity/sedentary behavior and provide guidance that promotes active lifestyles. A longitudinal study is needed to shed light on the unique contribution of asthma separated from the effects of overweight/obesity on physical activity and sedentary behaviors.

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Section: Introductionmentioning

confidence: 99%

Relationships among obesity, physical activity and sedentary behavior in young adolescents with and without lifetime asthma

2015

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“…Because of the close proximity of the developing airways and vasculature in the lung, vascular mediators have been suggested to influence pulmonary development. For instance, Chen and colleagues (2) and Schwarz and colleagues (3)(4)(5) used a mouse fetal lung allograft model to show that endothelial-monocyte activating polypeptide II can not only inhibit neovascularization, but can also significantly impair epithelial morphogenesis. Based on these and similar findings, our laboratory has focused on the role of vascular mediators during pulmonary development.…”

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Ephrin-B2 Reverse Signaling Increases α5β1 Integrin–Mediated Fibronectin Deposition and Reduces Distal Lung Compliance

Bennett

Afanador

Lal

et al. 2013

Am J Respir Cell Mol Biol

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Alveolar growth abnormalities and severe respiratory dysfunction are often fatal. Identifying mechanisms that control epithelial proliferation and enlarged, poorly septated airspaces is essential in developing new therapies for lung disease. The membrane-bound ligand ephrin-B2 is strongly expressed in lung epithelium, and yet in contrast to its known requirement for arteriogenesis, considerably less is known regarding the function of this protein in the epithelium. We hypothesize that the vascular mediator ephrin-B2 governs alveolar growth and mechanics beyond the confines of the endothelium. We used the in vivo manipulation of ephrin-B2 reverse signaling to determine the role of this vascular mediator in the pulmonary epithelium and distal lung mechanics. We determined that the ephrin-B2 gene (EfnB2) is strongly expressed in alveolar Type 2 cells throughout development and into adulthood. The role of ephrin-B2 reverse signaling in the lung was assessed in Efnb2LacZ/6YFDV mutants that coexpress the intracellular truncated ephrin-B2-b-galactosidase fusion and an intracellular point mutant ephrin-B2 protein that is unable to become tyrosine-phosphorylated or to interact with either the SH2 or PDZ domain-containing downstream signaling proteins. In these viable mice, we observed pulmonary hypoplasia and altered pulmonary mechanics, as evidenced by a marked reduction in lung compliance. Associated with the reduction in lung compliance was a significant increase in insoluble fibronectin (FN) basement membrane matrix assembly with FN deposition, and a corresponding increase in the a5 integrin receptor required for FN fibrillogenesis. These experiments indicate that ephrin-B2 reverse signaling mediates distal alveolar formation, fibrillogenesis, and pulmonary compliance.Keywords: arterial; fibronectin; a5b1 integrin; alveoli; pulmonary mechanics Lung development in mammalian species occurs through a series of overlapping stages, distinguished in terms of their histological appearance, and specifically the growth and differentiation of pulmonary epithelial structures. Although the proximal airways are completely formed by the end of gestation, the distal airways and alveoli continue their growth and maturation beyond the time of birth. Concurrent to the development of the epithelial structures, the pulmonary vasculature develops in a sequential fashion, via the coordinated processes of angiogenesis and vasculogenesis (1). Because of the close proximity of the developing airways and vasculature in the lung, vascular mediators have been suggested to influence pulmonary development. For instance, Chen and colleagues (2) and Schwarz and colleagues (3-5) used a mouse fetal lung allograft model to show that endothelial-monocyte activating polypeptide II can not only inhibit neovascularization, but can also significantly impair epithelial morphogenesis. Based on these and similar findings, our laboratory has focused on the role of vascular mediators during pulmonary development.Our studies have focused on the ephrin-B2 (EfnB2)...

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“…AEC II can proliferate into new AEC II and transdifferentiate into AEC I (1, 24). Following lung injury, AEC II-to-AEC I transdifferentiation is an important mechanism in injury repair (16,24,39). Tight junctions between epithelial cells regulate diffusion of solutes through the paracellular pathway (47, 61).…”

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Hyperoxia stimulates the transdifferentiation of type II alveolar epithelial cells in newborn rats

Hou

Yang

et al. 2015

American Journal of Physiology-Lung Cellular and Molecular Phys

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-Supplemental oxygen treatment in preterm infants may cause bronchopulmonary dysplasia (BPD), which is characterized by alveolar simplification and vascular disorganization. Despite type II alveolar epithelial cell (AEC II) damage being reported previously, we found no decrease in the AEC II-specific marker, surfactant protein C (SP-C), in the BPD model in our previous study. We thus speculated that AEC II injury is not a unique mechanism of BPD-related pulmonary epithelial repair dysfunction and that abnormal transdifferentiation can exist. Newborn rats were randomly assigned to model (85% oxygen inhalation) and control groups (room air inhalation). Expressions of AEC I (aquaporin 5, T1␣) and AEC II markers (SP-C, SP-B) were detected at three levels: 1) in intact lung tissue, 2) in AEC II isolated from rats in the two groups, and 3) in AEC II isolated from newborn rats, which were further cultured under either hyperoxic or normoxic conditions. In the model group, increased AEC I was observed at both the tissue and cell level, and markedly increased transdifferentiation was observed by immunofluorescent double staining. Transmission electron microscopy revealed morphological changes in alveolar epithelium such as damaged AECs, a fused air-blood barrier structure, and opened tight junctions in the model group. These findings indicate that transdifferentiation of AECs is not suppressed but rather is increased under hyperoxic treatment by compensation; however, such repair during injury cannot offset pulmonary epithelial air exchange and barrier dysfunction caused by structural damage to AECs. transdifferentiation; alveolar epithelial cells; hyperoxia; bronchopulmonary dysplasia SUPPLEMENTAL OXYGEN TREATMENT, which is often necessary for preterm infants with respiratory failure, has become a major risk factor for bronchopulmonary dysplasia (BPD), one of the most common, serious complications in preterm infants (6,34). BPD is characterized by high morbidity in infants with very low birth weight (BW Ͻ 1,500 g) soon after birth and may induce multiple complications in respiratory and nervous systems during adolescence (4, 6). Despite several decades of research, the underlying pathophysiological foundation of BPD has not been completely clarified.Lung tissue consists of many different cell types, and a developmental disorder of alveolar epithelial cells (AEC) is likely a major cause of BPD (40). The alveolar area accounts for Ն99% of the internal surface area of the lungs (49). Mammals have two types of AECs that maintain normal air exchange function by mutual coordination. Type I AEC (AEC I) cover nearly 96% of alveolar spaces and closely adhere to adjacent capillaries. Such cells are the main epithelial constituents of the air-blood barrier (18, 53) and have air exchange functions. Recent studies have revealed that AEC I can also secrete transport proteins to maintain intrapulmonary fluid and electrolyte balance (9,19,22). Type II AEC (AEC II) are located at the corners of alveoli and are more abundant than AEC I bu...

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Endothelial-monocyte activating polypeptide II disrupts alveolar epithelial type II to type I cell transdifferentiation

Cited by 45 publications

References 46 publications

Relationships among obesity, physical activity and sedentary behavior in young adolescents with and without lifetime asthma

Relationships among obesity, physical activity and sedentary behavior in young adolescents with and without lifetime asthma

Ephrin-B2 Reverse Signaling Increases α5β1 Integrin–Mediated Fibronectin Deposition and Reduces Distal Lung Compliance

Hyperoxia stimulates the transdifferentiation of type II alveolar epithelial cells in newborn rats

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