The early responses of VEGF and its receptors during acute lung injury: implication of VEGF in alveolar epithelial cell survival

Mura, Marco; Han, Bing; Andrade, Cristiano Feijó; Seth, Rashmi; Hwang, David; Waddell, Thomas K.; Keshavjee, Shaf; Liu, Mingyao

doi:10.1186/cc5042

Cited by 69 publications

(43 citation statements)

References 51 publications

(63 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Prior data from our laboratory and others demonstrated an association between increased VEGF and enhanced permeability in animal models of ischemia-reperfusion-, LPS-, and VEGF overexpression-mediated acute lung injury (24, 52-56), and increased IL-6 and VEGF have been linked with vascular leak in several systemic clinical disorders (29-32). Conversely, other published reports suggest that increased VEGF attenuated acute lung injury in animal models of hyperoxic-, intestinal ischemia-reperfusion-and LPS-induced lung damage (57-59), and human ARDS (60, 61). Few animal or human studies of acute lung injury have simultaneously measured BAL and tissue VEGF concentrations.…”

Section: Discussionmentioning

confidence: 89%

Interleukin-6 mediates pulmonary vascular permeability in a two-hit model of ventilator-associated lung injury

Gürkan

Zielinski

et al. 2011

Experimental Lung Research

View full text Add to dashboard Cite

To test the hypothesis that IL-6 contributes to the development of ventilator-associated lung injury (VALI), IL-6-deficient (IL6−/−) and wild-type control (WT) mice received intratracheal hydrochloric acid followed by randomization to MV (MV+IT HCl) or spontaneous ventilation (IT HCl). After 4 hr, injury was assessed by estimation of lung lavage protein concentration and total and differential cell counts, wet/dry lung weight ratio, pulmonary cell death, histologic inflammation score (LIS), and parenchymal myeloperoxidase (MPO) concentration. Vascular endothelial growth factor (VEGF) concentration was measured in lung lavage and homogenate, as IL-6 and stretch both regulate expression of this potent mediator of permeability. MV-induced increases in alveolar barrier dysfunction and lavage VEGF were attenuated in IL6−/− mice as compared with WT controls, whereas tissue VEGF concentration increased. The effects of IL-6 deletion on alveolar permeability and VEGF concentration were inflammation-independent, as parenchymal MPO concentration, LIS, and lavage total and differential cell counts did not differ between WT and IL6−/− mice following IT HCl+MV. These data support a role for IL-6 in promoting VALI in this two-hit model. Strategies to interfere with IL-6 expression or signaling may represent important therapeutic targets to limit the injurious effects of MV in inflamed lungs.

show abstract

Section: Discussionmentioning

confidence: 89%

Interleukin-6 mediates pulmonary vascular permeability in a two-hit model of ventilator-associated lung injury

Gürkan

Zielinski

et al. 2011

Experimental Lung Research

View full text Add to dashboard Cite

show abstract

“…These are poorly understood in the context of lung injury, but it is reasonable to infer functional significance (presented in the Discussion). In order to validate select transcripts, we performed qRT-PCR on Fas and Vegfa , both of which represent differentially expressed transcripts in the array that are recognized as important modulators of both cell death and lung injury (36, 37). Gene expression changes measured by qRT-PCR were consistent with those identified by microarray (Figure 6C–D).…”

Section: Resultsmentioning

confidence: 99%

“…For example, Fas expression, which can directly elicit epithelial apoptosis and lung injury (36), was significantly higher in the absence of LIF. Likewise, VEGF, which is both STAT3-dependent (50) and protective during lung injury (37), was decreased in the lungs following LIF neutralization. For more unbiased perspectives on LIF-dependent gene changes, we assembled lists of the 10 most up- and down-regulated transcripts in LIF-deficient injured lungs.…”

Section: Discussionmentioning

confidence: 99%

Leukemia Inhibitory Factor Signaling Is Required for Lung Protection during Pneumonia

Quinton

Mizgerd

Hilliard

et al. 2012

The Journal of Immunology

View full text Add to dashboard Cite

Lung infections represent a tremendous disease burden and a leading cause of acute lung injury. STAT3 signaling is essential for controlling lung injury during pneumonia. We previously identified leukemia inhibitory factor (LIF) as a prominent STAT3-activating cytokine expressed in the airspaces of pneumonic lungs, but its physiological significance in this setting has never been explored. To do so, Escherichia coli was intratracheally instilled into C57BL/6 mice in the presence of neutralizing anti-LIF IgG or control IgG. Anti-LIF completely eliminated lung LIF detection and markedly exacerbated lung injury compared to control mice as evidenced by airspace albumin content, lung liquid accumulation, and histological analysis. Although lung bacteriology was equivalent between groups, bacteremia was more prevalent with anti-LIF treatment, suggestive of compromised barrier function rather than impaired antibacterial defense as the cause of dissemination. Inflammatory cytokine expression was also exaggerated in anti-LIF-treated lungs, albeit after injury had ensued. Interestingly, alveolar neutrophil recruitment was modestly but significantly reduced compared to control mice despite elevated cytokine levels, indicating that inflammatory injury was not a consequence of excessive neutrophilic alveolitis. Lastly, the lung transcriptome was dramatically remodeled during pneumonia, but far more so following LIF neutralization, with gene changes implicating cell death and epithelial homeostasis amongst other processes relevant to tissue injury. From these findings, we conclude that endogenous LIF facilitates tissue protection during pneumonia. The LIF-STAT3 axis is here identified as a critical determinant of lung injury with clinical implications for pneumonia patients.

show abstract

“…It has been proposed that it may function as a survival factor for both epithelial cells [80,81] and ECs [82] in the normal lung, possibly acting in an autocrine fashion on epithelial cells [81] and modulating the functions of the adjacent vascular endothelium in a paracrine manner [83]. The VEGF survival signal in both ECs and epithelial cells is in part mediated through the phosphatidylinositol 3-kinase/Akt signal transduction pathway [81,82].…”

Section: Vegf In Lung Maintenancementioning

confidence: 99%

“…It remains to be established, however, whether enhanced VEGF expression in the fibroproliferative/recovery phases of ARDS/ALI represents a marker of resolution or is actively participating in the repair process [80,84,87,92,94,133,135]. …”

Section: Vegf In Resolution/repair From Ardsmentioning

confidence: 99%

Vascular Endothelial Growth Factor in Acute Lung Injury and Acute Respiratory Distress Syndrome

Barratt

Medford²,

Millar³

2013

Respiration

View full text Add to dashboard Cite

Acute respiratory distress syndrome (ARDS) is the most severe form of lung injury, characterised by alveolar oedema and vascular permeability, in part due to disruption of the alveolar capillary membrane integrity. Vascular endothelial growth factor (VEGF) was originally identified as a vascular permeability factor and has been implicated in the pathogenesis of acute lung injury/ARDS. This review describes our current knowledge of VEGF biology and summarises the literature investigating the potential role VEGF may play in normal lung maintenance and in the development of lung injury.

show abstract

The early responses of VEGF and its receptors during acute lung injury: implication of VEGF in alveolar epithelial cell survival

Abstract: Introduction The function of the vascular endothelial growth factor (VEGF) system in acute lung injury (ALI) is controversial. We hypothesized that the role of VEGF in ALI may depend upon the stages of pathogenesis of ALI.

Cited by 69 publications

References 51 publications

Interleukin-6 mediates pulmonary vascular permeability in a two-hit model of ventilator-associated lung injury

Interleukin-6 mediates pulmonary vascular permeability in a two-hit model of ventilator-associated lung injury

Leukemia Inhibitory Factor Signaling Is Required for Lung Protection during Pneumonia

Vascular Endothelial Growth Factor in Acute Lung Injury and Acute Respiratory Distress Syndrome

Contact Info

Product

Resources

About