COVID-19 Biogenesis and Intracellular Transport

Mirоnоv, Alexander A.; Савин, М А; Beznoussenko, Galina V.

doi:10.3390/ijms24054523

Cited by 11 publications

(8 citation statements)

References 217 publications

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“…While hAMECs showed substrate-specific transport of only the BODIPY-FA tracer, hCMECs co-transported BODIPY-FA and dextran non-selectively, most likely within clathrin-coated transport vesicles judging from treatment with endocytotic inhibitors. This is not surprising, as clathrin-dependent transcytosis is considered the main vesicle-mediated uptake pathway for continuous endothelium (16). Inhibition of clathrins reduced hCMEC fatty acid transcytosis and increased their TEER.…”

Section: Discussionmentioning

confidence: 99%

“…Based on literature it was instead more surprising that the data presented in Fig.4 suggest hAMECs to use caveolae for fatty acid uptake (16). Both the adipose and heart microvasculature is very rich in caveolae, but these vesicles have by some been suggested to mostly conform a structural storage site for endothelial cholesterol, and not engage in endocytosis.…”

Section: Discussionmentioning

confidence: 99%

“…Because both hAMECs and hCMECs harbor caveolae, and their uncertain role in fatty acid transcytosis, we conclude that the vesicular mechanism mediating substrate specificity for the adipose endothelium remains to be determined, despite the apparent EC-specific pattern of inhibitor-sensitivity to caveolar transport. The involvement of specific fatty acid transporters should also be investigated since these receptors can reside inside budding sites of endocytic vesicles (16, 18, 19). For instance, our system could be utilized in combination with genetic knockdown of the CD36-inhibitor Sulfo-N-succinimidyl oleate (SSO) (15, 20) or molecules that inhibit mitochondrial ATP production (21).…”

Section: Discussionmentioning

confidence: 99%

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Adipose tissue microvascular endothelial cells form a tight vascular barrier that selectively transcytoses fatty acid tracers

Schipper,

Ioannidou,

Maestri

et al. 2024

Preprint

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In organs with continuous, non-leaky capillaries like white adipose tissue and the heart, microvascular endothelial cells (ECs) serve as a vital barrier, facilitating nutrient delivery to underlying tissues. While capillary heterogeneity between organs is well established, how these vascular layers have adapted their key functions - such as fatty acid transport - to their respective organs remains unclear, largely due to the lack of organotypic endothelial model systems. Here we demonstrate that the vascular barrier in white adipose tissue, a crucial organ for whole-body fatty acid handling, exhibits comparable impermeability to that of heart and muscle. To investigate if the adipose endothelium possesses tissue-specific functions for facilitating fatty acid transport, we developed an in vitro dual tracing-system that allows simultaneous monitoring of barrier integrity and fatty acid transport dynamics by modifying the classic transwell culture. Using this system, we can show human adipose-derived primary ECs selectively transport fluorescent fatty acid tracers while excluding other tracers like dextrans, a phenomenon not observed in other cultured human ECs. Additionally, our findings reveal EC-type specific responses to various transcytosis inhibitors. Our results underscore the unique characteristics of the adipose endothelium and enhances our understanding of how microvascular permeability and transport dynamics have adapted to their specific organ physiology.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Adipose tissue microvascular endothelial cells form a tight vascular barrier that selectively transcytoses fatty acid tracers

Schipper,

Ioannidou,

Maestri

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…Then SARS-CoV-2 starts to use the protein machines of host cells and their membranes for its biogenesis. Glycosylated viral particles are produced through endoplasmic reticulum, Golgi apparatus and other organelles, and eventually secreted into the airway [44] .…”

Section: Discussionmentioning

confidence: 99%

Comprehensive analysis of immunogenic cell death-related gene and construction of prediction model based on WGCNA and multiple machine learning in severe COVID-19

Li,

wu,

yang

et al. 2023

Preprint

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Severe Acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) is a highly transmissible and pathogenic coronavirus that emerged in late 2019 and has caused a pandemic of acute respiratory disease with a high mortality rate. The death of coronavirus disease 2019 (COVID-19) is primarily due to from critically ill patients, especially from ARDS complications caused by SARS-CoV-2. Therefore, it is essential to contribute an in-depth understanding of the pathogenesis of the disease and to identify biomarkers for predicting critically ill patients at the molecular level, and thereby reduce COVID-19 mortality. Immunogenic cell death (ICD), as a specific variant of regulatory cell death driven by stress, can induce adaptive immune responses against cell death antigens in the host. Studies have confirmed that both innate and adaptive immune pathways are involved in the pathogenesis of SARS-CoV-2 infection. In severe COVID-19 patients, a large number of inflammatory mediators are released and cell death occurs, which leads to immune disorders. However, the role of ICD in the pathogenesis of severe COVID-19 has rarely been explored. In this study, we systematically evaluated the role of ICD-related genes in COVID-19. The differential expression of ICD-related genes in COVID-19 samples and healthy control samples, as well in ICU samples and Non-ICU samples were respectively explored. We conducted consensus clustering, immune infiltration analysis, and functional enrichment analysis based on ICD differentially expressed genes. The results showed that immune infiltration characteristics were altered in severe and non-severe COVID-19. In addition, we used multiple machine learning methods to screen for five risk genes (KLF5, BICDL1, APH1B, GRB10, and OLAH), which are used to predict COVID-19 severity. Finally, we constructed a nomogram to predict the risk of severe COVID-19 based on the classification and recognition model, and validated the model with external data sets. This study provides a valuable direction for the exploration of the pathogenesis and progress of COVID-19, and helps in the early identification of severe cases of COVID-19 to reduce mortality.

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“…Intracellular membrane trafficking is likely to play an important role in modulating ALK1 signaling and synergy under SS [72]. EC barrier functions are sensitive to large disruptions in membrane trafficking, such as intercellular junctional permeability [73].…”

Section: Alk1-mediated Mechanosensing Is Regulated Via Various Pathwa...mentioning

confidence: 99%

Shear stress and very low levels of ligand synergize to activate ALK1 signaling in endothelial cells

Cheng,

Anzell,

Schwartze

et al. 2023

Preprint

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Endothelial cells (ECs) respond to concurrent stimulation by biochemical fac-tors and wall shear stress (SS) exerted by blood flow. Disruptions in flow-induced responses can result in remodeling issues and cardiovascular diseases, but the detailed mechanisms linking flow-mechanical cues and biochemical signaling remain unclear. Activin receptor-like kinase 1 (ALK1) integrates SS and ALK1-ligand cues in ECs; ALK1 mutations cause hereditary hemorrhagic telangiectasia (HHT), marked by arteriovenous malformation (AVM) development. However, the mechanistic underpinnings of ALK1 signaling modulation by fluid flow and the link to AVMs remain uncertain. We recorded EC responses under varying SS magnitudes and ALK1 ligand concentrations by assaying pSMAD1/5/9 nuclear localization using a custom multi-SS microfluidic device and a custom image analysis pipeline. We extended the previously reported syn-ergy between SS and BMP9, to include BMP10 and BMP9/10 . Moreover, we demonstrated this synergy is effective even at extremely low SS magnitudes (0.4 dyn/cm2) and ALK1 ligand range (femtogram/mL). The synergistic response to ALK1 ligands and SS requires the kinase activity of ALK1. Moreover, ALK1’s basal activity and response to minimal ligand levels depend on endo-cytosis, distinct from cell-cell junctions, cytoskeleton-mediated mechanosensing, or cholesterol-enriched microdomains. Yet, an in-depth comprehension of ALK1 receptor trafficking’s molecular mechanisms requires further investigation.

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COVID-19 Biogenesis and Intracellular Transport

Cited by 11 publications

References 217 publications

Adipose tissue microvascular endothelial cells form a tight vascular barrier that selectively transcytoses fatty acid tracers

Adipose tissue microvascular endothelial cells form a tight vascular barrier that selectively transcytoses fatty acid tracers

Comprehensive analysis of immunogenic cell death-related gene and construction of prediction model based on WGCNA and multiple machine learning in severe COVID-19

Shear stress and very low levels of ligand synergize to activate ALK1 signaling in endothelial cells

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