scholarly journals Hypoxia-Inducible Factor Signaling in Inflammatory Lung Injury and Repair

Cells ◽  
2022 ◽  
Vol 11 (2) ◽  
pp. 183
Author(s):  
Colin E. Evans
Keyword(s):  
Transcription Factors ◽  
Lung Injury ◽  
Target Genes ◽  
Alveolar Epithelial Cell ◽  
Hypoxia Inducible Factor ◽  
Cell Types ◽  
Vascular Repair ◽  
Alveolar Epithelial ◽  
Injury And Repair ◽  
Target Side

Inflammatory lung injury is characterized by lung endothelial cell (LEC) death, alveolar epithelial cell (AEC) death, LEC–LEC junction weakening, and leukocyte infiltration, which together disrupt nutrient and oxygen transport. Subsequently, lung vascular repair is characterized by LEC and AEC regeneration and LEC–LEC junction re-annealing, which restores nutrient and oxygen delivery to the injured tissue. Pulmonary hypoxia is a characteristic feature of several inflammatory lung conditions, including acute lung injury (ALI), acute respiratory distress syndrome (ARDS), and severe coronavirus disease 2019 (COVID-19). The vascular response to hypoxia is controlled primarily by the hypoxia-inducible transcription factors (HIFs) 1 and 2. These transcription factors control the expression of a wide variety of target genes, which in turn mediate key pathophysiological processes including cell survival, differentiation, migration, and proliferation. HIF signaling in pulmonary cell types such as LECs and AECs, as well as infiltrating leukocytes, tightly regulates inflammatory lung injury and repair, in a manner that is dependent upon HIF isoform, cell type, and injury stimulus. The aim of this review is to describe the HIF-dependent regulation of inflammatory lung injury and vascular repair. The review will also discuss potential areas for future study and highlight putative targets for inflammatory lung conditions such as ALI/ARDS and severe COVID-19. In the development of HIF-targeted therapies to reduce inflammatory lung injury and/or enhance pulmonary vascular repair, it will be vital to consider HIF isoform- and cell-specificity, off-target side-effects, and the timing and delivery strategy of the therapeutic intervention.

scholarly journals Tumor necrosis factor-α small interfering RNA alveolar epithelial cell-targeting nanoparticles reduce lung injury in C57BL/6J mice with sepsis

2021 ◽  
Vol 49 (1) ◽  
pp. 030006052098465
Author(s):  
Like Qian ◽  
Xi Yin ◽  
Jiahao Ji ◽  
Zhengli Chen ◽  
He Fang ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Epithelial Cell ◽  
Lung Injury ◽  
Tumor Necrosis ◽  
Alveolar Epithelial Cell ◽  
Weight Ratio ◽  
B Cell Lymphoma ◽  
Alveolar Epithelial ◽  
Tnf Α ◽  
Necrosis Factor

Background The role of tumor necrosis factor (TNF)-α small interfering (si)RNA alveolar epithelial cell (AEC)-targeting nanoparticles in lung injury is unclear. Methods Sixty C57BL/6J mice with sepsis were divided into normal, control, sham, 25 mg/kg, 50 mg/kg, and 100 mg/kg siRNA AEC-targeting nanoparticles groups (n = 10 per group). The wet:dry lung weight ratio, and hematoxylin and eosin staining, western blotting, and enzyme-linked immunosorbent assays for inflammatory factors were conducted to compare differences among groups. Results The wet:dry ratio was significantly lower in control and sham groups than other groups. TNF-α siRNA AEC-targeting nanoparticles significantly reduced the number of eosinophils, with significantly lower numbers in the 50 mg/kg group than in 25 mg/kg and 100 mg/kg groups. The nanoparticles also significantly reduced the expression of TNF-α, B-cell lymphoma-2, caspase 3, interleukin (IL)-1β, and IL-6, with TNF-α expression being significantly lower in the 50 mg/kg group than in 25 mg/kg and 100 mg/kg groups. Conclusion TNF-α siRNA AEC-targeting nanoparticles appear to be effective at improving lung injury-related sepsis, and 50 mg/kg may be a preferred dose option for administration.

scholarly journals IL-17 mediated macrophage polarization increased inflammatory damage in SWI-ALI models

2020 ◽  
Author(s):  
Jiayi Zhao ◽  
Jin Pu ◽  
Rong Zhang ◽  
Jian Fan ◽  
Yiping Han ◽  
...  
Keyword(s):  
Wound Healing ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Alveolar Epithelial Cell ◽  
Macrophage Polarization ◽  
Alveolar Epithelial Cells ◽  
In Vitro Test ◽  
Alveolar Epithelial ◽  
Inflammatory Damage

Abstract BackgroundSeawater inhalation induced acute lung injury (SWI-ALI) is the common accident in daily naval training. To investigate the mechanism of SWI-ALI will help to improve the treatment effect. Alveolar macrophages (AM) is the majority of alveolar, also paly the key role in SWI-ALI repair. IL-17 also paly the key role in the innate immunity process.MethodIn this study, we used seawater induced the ALI in mouse model. And the lungs and serum were exacted at D1, D3, D7 and D14. The AM polarization were tested by flow cytometry. The IL-17 concentration were tested by ELISA. Then the IL-17 function were confirmed by in vitro test. The mouse alveolar epithelial cell and mouse AM were co-cultured. The test compared the wound healing effect of MAE with and without IL-17.ResultThe AM switch into M1 and IL-17A increased were found after seawater dosing. And the IL-17a supplement attenuated wound healing of alveolar epithelial cells through improve the polarization of AM were confirmed in vitro model.ConclusionThe high IL-I7 micro-environment will increased the inflammatory damage through induced macrophage polarization in acute lung injury. The IL-17 antagonists have the potential to increase clinical effect in SWI-ALI treatment.

scholarly journals Noncanonical WNT-5A signaling impairs endogenous lung repair in COPD

2016 ◽  
Vol 214 (1) ◽  
pp. 143-163 ◽  
Author(s):  
Hoeke A. Baarsma ◽  
Wioletta Skronska-Wasek ◽  
Kathrin Mutze ◽  
Florian Ciolek ◽  
Darcy E. Wagner ◽  
...  
Keyword(s):  
Epithelial Cell ◽  
Target Genes ◽  
Alveolar Epithelial Cell ◽  
Lung Fibroblasts ◽  
Chronic Obstructive ◽  
Pathological Feature ◽  
Tissue Destruction ◽  
Alveolar Epithelial ◽  
Lung Repair

Chronic obstructive pulmonary disease (COPD) is a leading cause of death worldwide. One main pathological feature of COPD is the loss of functional alveolar tissue without adequate repair (emphysema), yet the underlying mechanisms are poorly defined. Reduced WNT–β-catenin signaling is linked to impaired lung repair in COPD; however, the factors responsible for attenuating this pathway remain to be elucidated. Here, we identify a canonical to noncanonical WNT signaling shift contributing to COPD pathogenesis. We demonstrate enhanced expression of noncanonical WNT-5A in two experimental models of COPD and increased posttranslationally modified WNT-5A in human COPD tissue specimens. WNT-5A was increased in primary lung fibroblasts from COPD patients and induced by COPD-related stimuli, such as TGF-β, cigarette smoke (CS), and cellular senescence. Functionally, mature WNT-5A attenuated canonical WNT-driven alveolar epithelial cell wound healing and transdifferentiation in vitro. Lung-specific WNT-5A overexpression exacerbated airspace enlargement in elastase-induced emphysema in vivo. Accordingly, inhibition of WNT-5A in vivo attenuated lung tissue destruction, improved lung function, and restored expression of β-catenin–driven target genes and alveolar epithelial cell markers in the elastase, as well as in CS-induced models of COPD. We thus identify a novel essential mechanism involved in impaired mesenchymal–epithelial cross talk in COPD pathogenesis, which is amenable to therapy.

scholarly journals Activation of Hypoxia-Inducible Factor-1α in Type 2 Alveolar Epithelial Cell Is a Major Driver of Acute Inflammation Following Lung Contusion*

2014 ◽  
Vol 42 (10) ◽  
pp. e642-e653 ◽  
Author(s):  
Madathilparambil V. Suresh ◽  
Sadeesh Kumar Ramakrishnan ◽  
Bivin Thomas ◽  
David Machado-Aranda ◽  
Yu Bi ◽  
...  
Keyword(s):  
Epithelial Cell ◽  
Acute Inflammation ◽  
Alveolar Epithelial Cell ◽  
Hypoxia Inducible Factor ◽  
Lung Contusion ◽  
Hypoxia Inducible Factor 1Α ◽  
Alveolar Epithelial

PMNS EXACERBATE HYPEROXIC LUNG INJURY VIA AUGMENTED ALVEOLAR EPITHELIAL CELL DEATH.

Shock ◽  
2004 ◽  
Vol 21 ◽  
pp. 27
Author(s):  
L. Mantell ◽  
E. J. Miller ◽  
T. Sakuragi ◽  
J. Romashko ◽  
H. Zhu ◽  
...  
Keyword(s):  
Cell Death ◽  
Epithelial Cell ◽  
Lung Injury ◽  
Alveolar Epithelial Cell ◽  
Alveolar Epithelial ◽  
Hyperoxic Lung Injury ◽  
Epithelial Cell Death
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