Cell differentiation and aging accompanied by depletion of the ACE2 protein

Bártová, Eva; Legartová, Soňa; Krejčí, Jana; Arcidiacono, Orazio Angelo

doi:10.18632/aging.202221

Cited by 13 publications

(9 citation statements)

References 32 publications

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“…When we compared the ACE-2 expression on the hydrogel substrates, we observed a significant decrease in ACE-2 expression with increasing stiffness (Figure 4C,D). This correlates well with decreased expression of ACE-2 found in lungs of older rats, 54 which has also been shown in other tissues in mice 55 and agrees with our finding that cells on softer substrates showed more PV infection. Additionally, Calu3 cells express more ACE-2 on dense scaffolds than sparse fibers (Figure 4E,F) in an opposing trend to cell cluster size (Figure 3C).…”

Section: Ace-2 Expression Is Modulated By Cell−materials Interactionsupporting

confidence: 92%

Biomechanical Dependence of SARS-CoV-2 Infections

Paul

Kumar

Kaoud

et al. 2022

ACS Appl. Bio Mater.

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Older people have been disproportionately vulnerable to the current SARS-CoV-2 pandemic, with an increased risk of severe complications and death compared to other age groups. A mix of underlying factors has been speculated to give rise to this differential infection outcome including changes in lung physiology, weakened immunity, and severe immune response. Our study focuses on the impact of biomechanical changes in lungs that occur as individuals age, that is, the stiffening of the lung parenchyma and increased matrix fiber density. We used hydrogels with an elastic modulus of 0.2 and 50 kPa and conventional tissue culture surfaces to investigate how infection rate changes with parenchymal tissue stiffness in lung epithelial cells challenged with SARS-CoV-2 Spike (S) protein pseudotyped lentiviruses. Further, we employed electrospun fiber matrices to isolate the effect of matrix density. Given the recent data highlighting the importance of alternative virulent strains, we included both the native strain identified in early 2020 and an early S protein variant (D614G) that was shown to increase the viral infectivity markedly. Our results show that cells on softer and sparser scaffolds, closer resembling younger lungs, exhibit higher infection rates by the WT and D614G variant. This suggests that natural changes in lung biomechanics do not increase the propensity for SARS-CoV-2 infection and that other factors, such as a weaker immune system, may contribute to increased disease burden in the elderly.

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Section: Ace-2 Expression Is Modulated By Cell−materials Interactionsupporting

confidence: 92%

Biomechanical Dependence of SARS-CoV-2 Infections

Paul

Kumar

Kaoud

et al. 2022

ACS Appl. Bio Mater.

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“…Though ACE2 is known to be cell membrane protein, these results also show significant intracellular staining. Previous work has found ACE2 to be present in cell nuclei, where it may modulate gene expression 13. There is an expected degree of cytoplasmic expression of membrane proteins such as ACE2 as part of normal protein lysosomal degradation and recycling 13…”

Section: Discussionmentioning

confidence: 99%

“…13 There is an expected degree of cytoplasmic expression of membrane proteins such as ACE2 as part of normal protein lysosomal degradation and recycling. 13 Through its role as a negative regulator in the renin angiotensin aldosterone system, ACE2 helps limit inflammation and fibrosis by cleaving Angiotensin II and thus forming Angiotensin (1-7). Angiotensin (1-7) is a ligand for MAS1 receptors, which is known to then have vasodilatory and antifibrotic effects.…”

Section: Discussionmentioning

confidence: 99%

“…Previous work has found ACE2 to be present in cell nuclei, where it may modulate gene expression. 13 There is an expected degree of cytoplasmic expression of membrane proteins such as ACE2 as part of normal protein lysosomal degradation and recycling. 13 Through its role as a negative regulator in the renin angiotensin aldosterone system, ACE2 helps limit inflammation and fibrosis by cleaving Angiotensin II and thus forming Angiotensin (1-7).…”

Section: Discussionmentioning

confidence: 99%

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Angiotensin-converting Enzyme-2 (ACE2) Expression in Pediatric Liver Disease

Stevens

Kolachala

Joshi

et al. 2022

Applied Immunohistochemistry &Amp; Molecular Morphology

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The membrane protein angiotensin-converting enzyme-2 (ACE2) has gained notoriety as the receptor for severe acute respiratory syndrome coronavirus 2. Prior evidence has shown ACE2 is expressed within the liver but its function has not been fully discerned. Here, we utilized novel methodology to assess ACE2 expression in pediatric immune-mediated liver disease to better understand its presence in liver diseases and its role during infections such as COVID-19. We stained liver tissue with ACE2-specific immunofluorescent antibodies, analyzed via confocal microscopy. Computational deep learning-based segmentation models identified nuclei and cells, allowing the quantification of mean cellular and cytosolic immunofluorescent. Spatial transcriptomics provided high-throughput gene expression analysis in tissue to determine cellular composition for ACE2 expression. ACE2 plasma expression was quantified via enzyme-linked immunosorbent assay. High ACE2 expression was seen at the apical surface of cholangiocytes, with lower expression within hepatocyte cytosol and nonparenchymal cells (P < 0.001). Children with liver disease had higher ACE2 hepatic expression than pediatric control tissue (P < 0.001). Adult control tissue had higher expression than pediatric control (P < 0.001). Plasma ACE2 was not found to be statistically different between samples. Spatial transcriptomics identified cell composition of ACE2-expressing spots containing antibody-secreting cells. Our results show ACE2 expression throughout the liver, with strongest localization to cholangiocyte membranes. Machine learning can be used to rapidly identify hepatic cellular components for histologic analysis. ACE2 expression in the liver may be increased in pediatric liver disease. Future work is needed to better understand the role of ACE2 in chronic disease and acute infections.

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“…This type of cell line is based on previous studies that have analyzed the distribution of ACE2 in renal cell lines (HEK-293A). 17 To confirm the modulation of ACE2 was induced by the CDs, we further analyzed the interaction between ACE2 and CDs in molecular scope by computational analysis. The potential of CDs as ACE2 modulators will be revealed as a result of this research, and they will be able to be used as a treatment approach for ACE2-related pathological illnesses.…”

Section: Introductionmentioning

confidence: 99%

In Vitro and Silico Studies on the N-Doped Carbon Dots Potential in ACE2 Expression Modulation

et al. 2023

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The alteration of ACE2 expression level, which has been studied in many diseases, makes the topic of ACE2 inducer potential crucial to be explored. The ACE2 inducer could further be designed to control the ACE2 expression level, which is appropriate to a specific case. An in vitro study of well-characterized carbon dots (CDs), made from citric acid and urea, was performed to determine their ability to modulate the ACE2 receptor. Gene expression of ACE2 was quantified using concentrations adjusted for IC50 results from CDs viability assays in HEK 293 and A549 cell lines. RT-qPCR was used to assess the expression of the ACE2 gene and its induction effect in normal cell lines (HEK-293A). According to the results of the tests, ACE2 is expressed in HEK-293A cell lines, and diminazene aceturate can increase ACE2 expression. The effect of CDs on ACE2 gene expression was further examined on the cell lines that had previously been induced with diminazene aceturate, which resulted in upregulation of the ACE2 expression level. An in silico study has been done by using a molecular docking approach. The molecular docking results show that CDs can make strong interactions with ACE2 amino acid residues through hydrophobic interaction, π–π interaction, π-cation interaction, and ionic interaction.

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Cell differentiation and aging accompanied by depletion of the ACE2 protein

Cited by 13 publications

References 32 publications

Biomechanical Dependence of SARS-CoV-2 Infections

Biomechanical Dependence of SARS-CoV-2 Infections

Angiotensin-converting Enzyme-2 (ACE2) Expression in Pediatric Liver Disease

In Vitro and Silico Studies on the N-Doped Carbon Dots Potential in ACE2 Expression Modulation

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