AHR protects against lung vascular leakage in viral infection
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA938104 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR23601845_1.fastq.gz | Fastqsanger.gz | |||
| SRR23601845_2.fastq.gz | Fastqsanger.gz | |||
| SRR23601846_1.fastq.gz | Fastqsanger.gz | |||
| SRR23601846_2.fastq.gz | Fastqsanger.gz | |||
| SRR23601847_1.fastq.gz | Fastqsanger.gz |
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Project description:Disruption of the lung endothelial-epithelial cell barrier during respiratory virus infection causes cell and fluid accumulation in the air spaces and compromises vital gas exchange function. Endothelial cell dysfunction is known to exacerbate tissue damage; however, it is unclear whether the lung endothelium engages in tissue-protective activity during viral infection. Here we show that the environmental sensor aryl hydrocarbon receptor (AHR) is predominantly active in endothelial cells and protects against influenza-induced lung damage. Endothelial-specific AHR deletion caused increased vascular leakage in air spaces and enhanced influenza-induced lung tissue pathology. Global expression profiling revealed limited AHR-dependent regulation of vessels in the steady-state lung. However, following influenza-induced tissue damage and inflammation, AHR engages tissue-protective programmes in endothelia and prevents a dysplastic keratinised and apoptotic signature in the airways of infected lungs.
2023-05-23 | GSE203427 | GEO
Project description:We have identified the apelin-APJ axis as a mechanism of protection mediated by AHR signalling in lund=g endothelial cells. This RNAseq experiment will compare the effects of apelin receptor blockade on endothelial and epithelial responses in the lung during influenza infection.
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Project description:Aryl hydrocarbon receptor (AHR)-dependent protection against lung vascular leakage in viral infection
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Project description:Angiogenesis is an essential process in human physiology and disease pathology. Particularly, in ischemic disease condition, the proper induction of angiogenesis without vascular leakage will be crucial for its effective therapy. Ginsenosides, triterpenoid saponins from a well-known medicinal plant ginseng, have been considered as a strong candidate for modulating angiogenesis. However, the biologic activity of individual gensenoside compounds and their target pathway have not been elucidated systematically. To find the candidates of vascular-related therapeutic agents, we evaluated in vitro angiogenic efficacy of 10 ginsenosides using tube formation assay with human umbilical vein endothelial cells (HUVECs). Among them, F1 and Rh1 showed strong in vitro angiogenic properties including EC tube formation, proliferation, and migration similar to vascular endothelial growth factor (VEGF). However, RNA transcriptome analysis showed that F1 and Rh1 differentially regulate gene expressions in HUVECs compared to VEGF. Not only that, F1 and Rh1 significantly inhibited vascular endothelial growth factor (VEGF)-induced vascular leakage both in vitro and in vivo. From RNA transcriptome analysis, we identified that nuclear receptor subfamily 4 group A member 1 (NR4A1) is regulated by F1 and Rh1 for suppression of VEGF-induced vascular leakage. By suppressing the expression and transcriptional activity of NR4A1, F1 and Rh1 could stabilize the expression and localization of junctional vascular endothelial (VE)-cadherin. These findings demonstrate that F1 and Rh1 could be potential compounds in the development of vascular pharmaceuticals.
2019-03-20 | GSE116121 | GEO
Project description:Endothelial cells (ECs) form a tissue-specific barrier for disseminating cancer cells in distant organs. However, the molecular regulation of the ECs in the metastatic niche is poorly understood. Here, we analyzed the transcriptional reprogramming of ECs in the lung metastatic niche six hours after the arrival of melanoma cells in the niche. We discovered a novel EC cluster derived from venous capillaries in response to infiltrating cancer cells, which was enriched for cell-cell communication pathways, including the Dll4, Vegf and Il6-Jak-Stat pathways. The Jak-Stat activated oncogenic Pim3 kinase was a marker of the cancer responding ECs, being upregulated in spontaneous metastasis models and in ECs of human cancer. Notably, PIM inhibition increased vascular leakage and metastatic colonization in vivo and impaired the EC barrier via decreased junctional Cadherin-5 and catenins a, b and d. Thus, PIM3 protects the EC barrier in the metastatic niche, which may impair the efficacy of PIM inhibitors in cancer therapies.
2024-09-20 | GSE235394 | GEO
Project description:Endothelial cells (ECs) form a tissue-specific barrier for disseminating cancer cells in distant organs. However, the molecular regulation of the ECs in the metastatic niche is poorly understood. Here, we analyzed the transcriptional reprogramming of ECs in the lung metastatic niche six hours after the arrival of melanoma cells in the niche. We discovered a novel EC cluster derived from venous capillaries in response to infiltrating cancer cells, which was enriched for cell-cell communication pathways, including the Dll4, Vegf and Il6-Jak-Stat pathways. The Jak-Stat activated oncogenic Pim3 kinase was a marker of the cancer responding ECs, being upregulated in spontaneous metastasis models and in ECs of human cancer. Notably, PIM inhibition increased vascular leakage and metastatic colonization in vivo and impaired the EC barrier via decreased junctional Cadherin-5 and catenins a, b and d. Thus, PIM3 protects the EC barrier in the metastatic niche, which may impair the efficacy of PIM inhibitors in cancer therapies.
2024-09-20 | GSE253751 | GEO
Project description:Endothelial cells (ECs) form a tissue-specific barrier for disseminating cancer cells in distant organs. However, the molecular regulation of the ECs in the metastatic niche is poorly understood. Here, we analyzed the transcriptional reprogramming of ECs in the lung metastatic niche six hours after the arrival of melanoma cells in the niche. We discovered a novel EC cluster derived from venous capillaries in response to infiltrating cancer cells, which was enriched for cell-cell communication pathways, including the Dll4, Vegf and Il6-Jak-Stat pathways. The Jak-Stat activated oncogenic Pim3 kinase was a marker of the cancer responding ECs, being upregulated in spontaneous metastasis models and in ECs of human cancer. Notably, PIM inhibition increased vascular leakage and metastatic colonization in vivo and impaired the EC barrier via decreased junctional Cadherin-5 and catenins a, b and d. Thus, PIM3 protects the EC barrier in the metastatic niche, which may impair the efficacy of PIM inhibitors in cancer therapies.
2024-09-20 | GSE253749 | GEO
Project description:Pro-angiogenic Ginsenoside F1 and Rh1 Inhibit Vascular Leakage by Modulating NR4A1
| PRJNA477332 | ENA
Project description:Rationale: Aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor, has been considered as an important regulator for immune diseases. We have previously shown that AhR protects against allergic airway inflammation. The underlying mechanism, however, remains undetermined. Objectives: We sought to determine whether AhR specifically in Type II alveolar epithelial cells (AT2) modulates allergic airway inflammation and its underlying mechanisms. Methods: The role of AhR in AT2 cells in airway inflammation was investigated in a mouse model of asthma with AhR conditional knock out mice in AT2 cells (Sftpc-Cre;AhRflox/flox). The effect of AhR on allergen-induced autophagy was examined by both in vivo and in vitro analyses. The involvement of autophagy in airway inflammation was analyzed by using autophagy inhibitor chloroquine. The AhR-regulated gene profiling in AT2 cells was also investigated by RNA-seq analysis. Results: Sftpc-Cre; AhRflox/flox mice showed exacerbation of allergen-induced airway hyperresponsiveness and airway inflammation with elevated Th2 and airway epithelial-derived cytokines in bronchoalveolar lavage fluid (BALF). Notably, an increased allergen-induced autophagy was observed in the lung tissues of Sftpc-Cre; AhRflox/flox mice when compared with wild-type mice. Further analyses suggested a functional axis of AhR-TGF-β1 that is critical in driving allergic airway inflammation through regulating allergen-induced cellular autophagy. Furthermore, inhibition of autophagy suppressed allergic airway inflammation with decreased Th2 and epithelial cell-derived cytokines in BALFs. Additionally, RNA-seq analysis suggests that autophagy is one of the major pathways and CALCOCO2/NDP52 and S1009 are major autophagy-associated genes in AT2 cells that contribute to the AhR-mediated allergic airway inflammation. Conclusion: These results suggest that AhR in AT2 cells functions as a protective mechanism against allergic airway inflammation through controlling cell autophagy.
2022-06-13 | GSE205818 | GEO
Project description:Endothelial Pim3 kinase protects the vascular barrier during lung metastasis
| PRJNA985787 | ENA