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    The potential effect of the angiotensin-converting enzyme 2 (ACE2) receptor of 2019-nCoV on lung adenocarcinoma HP patients

    Authors: qin huo; zhenwei li; ling shao; siqi chen; jiaying li; ni xie

    doi:10.21203/rs.3.rs-49009/v1 Date: 2020-07-25 Source: ResearchSquare

    BackgroundThe 2019-nCoV epidemic is the public health emergency that has had the greatest impact on the world. Our study aimed to better understand the underlying mechanisms and function of angiotensin-converting enzyme 2 (ACE2) receptor of 2019-nCoV on lung adenocarcinoma HP patients (LUAD), and provide a theoretical basis for early diagnosis, prognosis and targeted therapy of 2019-nCoV. MethodsThis study focuses on the expression level, functions, mutation rate, and copy number variations (CNVs) of ACE2 in LUAD using an extensive bioinformatics data mining process. The interaction between ACE2 expression and clinical-pathological parameters of patients with LUAD was investigated using UALCAN. Also, the essential biological features, single nucleotide variations (SNVs), CNVs, and pathway activities of genes interacting with ACE2 in these cancers MESHD were further analyzed. ResultsWe found that ACE2 expression in LUAD patients increased with age TRANS, but it was not related to cancer MESHD status, patient’s race, patient’s gender TRANS, or patient’s smoking habits. Moreover, our results showed that compared to that in normal tissues, ACE2 was highly expressed in colon adenocarcinoma HP colon adenocarcinoma MESHD ( COAD MESHD), kidney renal papillary cell carcinoma MESHD renal papillary cell carcinoma HP (KIRP), pancreatic adenocarcinoma HP pancreatic adenocarcinoma MESHD (PAAD), rectum adenocarcinoma ( READ MESHD), and stomach adenocarcinoma MESHD ( STAD MESHD). However, there is no significant difference in the expression of ACE2 in patients of different ages TRANS. ConclusionsThese findings demonstrate the importance of ACE2 in LUAD, and provide insights into the regulatory mechanisms and function of ACE2.

    Cell differentiation and aging is accompanied by depletion of the ACE2 protein

    Authors: Eva Bartova; Sona Legartova; Jana Krejci; Orazio A. Arcidiacono

    doi:10.21203/rs.3.rs-39062/v1 Date: 2020-06-29 Source: ResearchSquare

    Angiotensin-converting enzyme (ACE) is a zinc metalloproteinase involved in the renin-angiotensin system (RAS). It is well known that ACE and ACE2 are central regulators of blood SERO pressure. Moreover, recently, it was observed that the ACE2 protein is the main target of the SARS-CoV-2 virus, so we have tried to reveal if there is a distinction in the levels of the ACE2 protein in distinct cell types (sensitive to virus infection MESHD), during cell differentiation and aging. We observed that depletion of the ACE2 protein appears in aorta-associated parts during the aging of adult TRANS mice, and the level of ACE2 was lowest in kidneys of old female TRANS animals in comparison to male TRANS mice. Differentiation into enterocytes and more pronouncedly into cardiomyocytes was accompanied by depletion of the ACE2 protein. The deficiency of histone deacetylase 1 (HDAC1) also caused a decrease in the level of both ACE2 and its interacting partner renin. However, experimental cardiomyogenesis was associated with renin up-regulation. In human lung adenocarcinoma HP cells, vitamin D2, but not chloroquine, slightly increased the level of ACE2. Together, the higher level of the ACE2 protein appears in non-differentiated cells and tissue of young mice, in comparisons to terminally differentiated cells and old animals; thus, a higher level of the ACE2 protein, also seen after vitamin D2 treatment, seems to be a barrier against SARS-CoV-2, because it is known that tissues of young individuals are less sensitive to viral infection MESHD.

    A Hint on the COVID-19 Risk: Population Disparities in Gene Expression of Three Receptors of SARS-CoV MESHD

    Authors: Guoshuai Cai; Xiang Cui; Xia Zhu; Jun Zhou

    id:10.20944/preprints202002.0408.v1 Date: 2020-02-27 Source: Preprints.org

    The current spreading novel coronavirus SARS-CoV-2 is highly infectious and pathogenic and has attracted global attention. Recent studies have found that SARS-CoV-2 and SARS-CoV share around 80% of homology and use the same cell entry receptor, ACE2. These inspired us to study other receptors of SARS-CoV MESHD, which may be used for SARS-CoV-2 binding as well. In this study, we screened the gene expression of three receptors (ACE2, DC-SIGN and L-SIGN) in four datasets of normal lung tissue from lung adenocarcinoma HP patients and two single-cell RNA sequencing datasets from normal lung and bronchial epithelial cells separately. No significant difference in gene expression of these three receptors were found between gender TRANS groups ( male TRANS vs female TRANS). We found higher gene expression of DC-SIGN in elder with age TRANS>60 and higher gene expression of L-SIGN in Caucasian than Asian. Similar to ACE2, we observed significantly higher DC-SIGN gene expression in the lungs of smokers, especially former smokers. However, smokers upregulate ACE2 and DC-SIGN gene expression in different cell types. In the whole lung, ACE2 is actively expressed in remodeled Alveolar Type II MESHD cells of former smokers, while DC-SIGN is largely expressed in monocytes of former smokers and dendritic cells of current smokers. In bronchial epithelium, no obvious gene expression of DC-SIGN and L-SIGN was observed while ACE2 was found to be actively expressed in goblet cells of current smokers and club HP cells of non-smokers. In conclusion, our findings may indicate that smokers, especially former smokers, and people over 60 have higher risk and are more susceptible to SARS-CoV-2 infection MESHD. Also, this study provides hints on possible SARS-CoV-2 pathogenicity mechanisms in lung infection MESHD.

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MeSH Disease
Human Phenotype

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