Lung injury after asphyxia and hemorrhagic shock in newborn piglets: Analysis of structural and inflammatory changes

Weber, Birte; Mendler, Marc Robin; Lackner, Ina; Zelewski, Alexander von; Höfler, Severin; Baur, Meike; Braun, Christian; Hummler, Helmut; Schwarz, Stephan; Preßmar, Jochen; Kalbitz, Miriam

doi:10.1371/journal.pone.0219211

Cited by 13 publications

(19 citation statements)

References 36 publications

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“…Except for postnatal day 3, claudin-18 expression first declines and then reaches a peak at postnatal on day 1 ( 27 ). In various animal models of lung injury, decreased expression of claudin-18 has been considered a sign of lung barrier damage ( 28 – 31 ). Especially in a model of hyperoxia-induced BPD, claudin-18 has been shown to possibly be involved in early pulmonary edema development and late alveolar development ( 32 ).…”

Section: Discussionmentioning

confidence: 99%

Claudin-18 expression under hyperoxia in neonatal lungs of bronchopulmonary dysplasia model rats

et al. 2022

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BackgroundBronchopulmonary dysplasia (BPD) is characterized by impaired alveolar and microvascular development. Claudin-18 is the only known lung-specific tight junction protein affecting the development and transdifferentiation of alveolar epithelium.ObjectiveWe aimed to explore the changes in the expression of claudin-18, podoplanin, SFTPC, and the canonical WNT pathway, in a rat model of hyperoxia-induced BPD, and to verify the regulatory relationship between claudin-18 and the canonical WNT pathway by cell experiments.MethodsA neonatal rat and cell model of BPD was established by exposing to hyperoxia (85%). Hematoxylin and eosin (HE) staining was used to confirm the establishment of the BPD model. The mRNA levels were assessed using quantitative real-time polymerase chain reaction(qRT-PCR). Protein expression levels were determined using western blotting, immunohistochemical staining, and immunofluorescence.ResultsAs confirmed by HE staining, the neonatal rat model of BPD was successfully established. Compared to that in the control group, claudin-18 and claudin-4 expression decreased in the hyperoxia group. Expression of β-catenin in the WNT signaling pathway decreased, whereas that of p-GSK-3β increased. Expression of the AEC II marker SFTPC initially decreased and then increased, whereas that of the AEC I marker podoplanin increased on day 14 (P < 0.05). Similarly, claudin-18, claudin-4, SFTPC and β-catenin were decreased but podoplanin was increased when AEC line RLE-6TN exposed to 85% hyperoxia. And the expression of SFTPC was increased, the podoplanin was decreased, and the WNT pathway was upregulated when claudin-18 was overexpressed.ConclusionsClaudin-18 downregulation during hyperoxia might affect lung development and maturation, thereby resulting in hyperoxia-induced BPD. Additionally, claudin-18 is associated with the canonical WNT pathway and AECs transdifferentiation.

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Section: Discussionmentioning

confidence: 99%

Claudin-18 expression under hyperoxia in neonatal lungs of bronchopulmonary dysplasia model rats

et al. 2022

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“…Except for postnatal day 3, claudin-18 expression declines then reaches a peak at postnatal day 15 (Lewis et al 2018). In various animal models of lung injury, decreased claudin-18 expression has been considered a sign of lung barrier damage (Lee et al 2020;M et al 2020;Reynolds et al 2018;Weber et al 2019). Especially in a hyperoxia-induced BPD model, claudin-18 may be involved in early pulmonary edema development and late alveolar development (Abdul-Hafez et al 2019).…”

Section: Discussionmentioning

confidence: 99%

Claudin-18 expression under hypoxia in neonatel lungs of brochopulmonary dysplasia model rats

Zuo

Tong

Yang

et al. 2021

Preprint

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Background: Bronchopulmonary dysplasia (BPD) is characterized by impaired alveolar and microvascular development. Claudin-18 is the only known lung-specific tight junction protein affecting alveolar epithelium development and transdifferentiation. Objective: To explore the changes in claudin-18 expression, alveolar epithelial cell (AEC) marker proteins, the canonical Wnt pathway, and their possible regulatory relationships in a hyperoxia-induced BPD rat model. Methods: The BPD neonatal rat model was established by exposure to hyperoxia (85%). Hematoxylin and eosin (HE) staining was used to confirm the establishment of the BPD model. The mRNA levels were assessed using quantitative real-time polymerase chain reaction, while protein expression levels were determined using western blotting, immunohistochemical staining, and immunofluorescence . Results: As confirmed by HE staining, the BPD neonatal rat model was successfully established. Compared with the air group, claudin-18 and claudin-4 expression decreased in the hyperoxia group. The expression of β-catenin of the Wnt signaling decreased, whereas that of p-GSK-3β increased. Expression of the AEC Ⅱ marker SFTPC decreased initially and then increased, whereas that of the AEC Ⅰ marker Podoplanin increased on day 14 (P < 0.05). Conclusions: Claudin-18 downregulation during hyperoxia may affect lung development and maturation, which may result in hyperoxia-induced BPD. Additionally, claudin-18 is associated with the canonical Wnt pathway and alveolar epithelial transdifferentiation.

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“…Hemorrhagic shock and ischemia/reperfusion-induced lung injury: Asphyxia-, hemorrhagic shock-, and ischemia/reperfusion-induced injury in pigs and rats, and primary human alveolar epithelial cells [219,220,221] Decrease in claudin-4, claudin-5, and claudin-18, ZO-1, occludin, and JAMA-1; increase in VE-cadherin activation; no change in claudin-3…”

Section: Role Of Tlr4 In Resistance To Corticosteroid Treatmentmentioning

confidence: 99%

Tight Junctions, the Epithelial Barrier, and Toll-like Receptor-4 During Lung Injury

et al. 2022

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Lung epithelium is constantly exposed to the environment and is critically important for the orchestration of initial responses to infectious organisms, toxins, and allergic stimuli, and maintenance of normal gaseous exchange and pulmonary function. The integrity of lung epithelium, fluid balance, and transport of molecules is dictated by the tight junctions (TJs). The TJs are formed between adjacent cells. We have focused on the topic of the TJ structure and function in lung epithelial cells. This review includes a summary of the last twenty years of literature reports published on the disrupted TJs and epithelial barrier in various lung conditions and expression and regulation of specific TJ proteins against pathogenic stimuli. We discuss the molecular signaling and crosstalk among signaling pathways that control the TJ structure and function. The Toll-like receptor-4 (TLR4) recognizes the pathogen-and damage-associated molecular patterns released during lung injury and inflammation and coordinates cellular responses. The molecular aspects of TLR4 signaling in the context of TJs or the epithelial barrier are not fully known. We describe the current knowledge and possible networking of the TLR4-signaling with cellular and molecular mechanisms of TJs, lung epithelial barrier function, and resistance to treatment strategies.

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Lung injury after asphyxia and hemorrhagic shock in newborn piglets: Analysis of structural and inflammatory changes

Cited by 13 publications

References 36 publications

Claudin-18 expression under hyperoxia in neonatal lungs of bronchopulmonary dysplasia model rats

Claudin-18 expression under hyperoxia in neonatal lungs of bronchopulmonary dysplasia model rats

Claudin-18 expression under hypoxia in neonatel lungs of brochopulmonary dysplasia model rats

Tight Junctions, the Epithelial Barrier, and Toll-like Receptor-4 During Lung Injury

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