1.A review on the role of angiotensin-converting enzyme 2 in children with coronavirus disease 2019.
Jing LIU ; Guo-Qian CHEN ; Li WEI ; Fu-Yong JIAO
Chinese Journal of Contemporary Pediatrics 2020;22(12):1344-1348
With the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) all over the world, there is an increasing number of children with such infection. Angiotensin-converting enzyme 2 (ACE2), one of the binding sites for SARS-CoV-2 infection in humans, can bind to viral spike proteins, allowing transmembrane serine protease (TMPRSS2) to activate S-protein to trigger infection and induce the production of various inflammatory factors such as interleukin-1, interferon-l, and tumor necrosis factor. Compared with adults, children tend to have lower expression levels of ACE2 and TMPRSS2, which are presumed to be associated with milder symptoms and fewer cases in children. The article summarizes the research advances in the role of ACE2 during SARS-CoV-2 infection, in order to help understand the pathogenic mechanism of SARS-CoV-2 and provide a reference for better development of drugs and vaccines to prevent and treat coronavirus disease 2019 in children.
Angiotensin-Converting Enzyme 2/metabolism*
;
COVID-19
;
Child
;
Humans
;
Receptors, Virus/metabolism*
;
SARS-CoV-2
;
Serine Endopeptidases/metabolism*
3.Single-cell analysis of angiotensin-converting enzyme II expression in human kidneys and bladders reveals a potential route of 2019 novel coronavirus infection.
Wei LIN ; Jue FAN ; Long-Fei HU ; Yan ZHANG ; Joshua D OOI ; Ting MENG ; Peng JIN ; Xiang DING ; Long-Kai PENG ; Lei SONG ; Rong TANG ; Zhou XIAO ; Xiang AO ; Xiang-Cheng XIAO ; Qiao-Ling ZHOU ; Ping XIAO ; Yong ZHONG
Chinese Medical Journal 2021;134(8):935-943
BACKGROUND:
Since 2019, a novel coronavirus named 2019 novel coronavirus (2019-nCoV) has emerged worldwide. Apart from fever and respiratory complications, acute kidney injury has been observed in a few patients with coronavirus disease 2019. Furthermore, according to recent findings, the virus has been detected in urine. Angiotensin-converting enzyme II (ACE2) has been proposed to serve as the receptor for the entry of 2019-nCoV, which is the same as that for the severe acute respiratory syndrome. This study aimed to investigate the possible cause of kidney damage and the potential route of 2019-nCoV infection in the urinary system.
METHODS:
We used both published kidney and bladder cell atlas data and new independent kidney single-cell RNA sequencing data generated in-house to evaluate ACE2 gene expression in all cell types in healthy kidneys and bladders. The Pearson correlation coefficients between ACE2 and all other genes were first generated. Then, genes with r values larger than 0.1 and P values smaller than 0.01 were deemed significant co-expression genes with ACE2.
RESULTS:
Our results showed the enriched expression of ACE2 in all subtypes of proximal tubule (PT) cells of the kidney. ACE2 expression was found in 5.12%, 5.80%, and 14.38% of the proximal convoluted tubule cells, PT cells, and proximal straight tubule cells, respectively, in three published kidney cell atlas datasets. In addition, ACE2 expression was also confirmed in 12.05%, 6.80%, and 10.20% of cells of the proximal convoluted tubule, PT, and proximal straight tubule, respectively, in our own two healthy kidney samples. For the analysis of public data from three bladder samples, ACE2 expression was low but detectable in bladder epithelial cells. Only 0.25% and 1.28% of intermediate cells and umbrella cells, respectively, had ACE2 expression.
CONCLUSION
This study has provided bioinformatics evidence of the potential route of 2019-nCoV infection in the urinary system.
Angiotensin-Converting Enzyme 2/metabolism*
;
COVID-19
;
Gene Expression
;
Humans
;
Kidney/metabolism*
;
SARS-CoV-2
;
Sequence Analysis, RNA
;
Single-Cell Analysis
;
Urinary Bladder/metabolism*
4.SARS-CoV-2 neutralizing monoclonal antibodies and nanobodies: a review.
Yulei CHEN ; Jinjin LIN ; Peiyi ZHENG ; Minjie CAO ; Tengchuan JIN
Chinese Journal of Biotechnology 2022;38(9):3173-3193
Coronavirus disease (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), with strong contagiousness, high susceptibility and long incubation period. cell entry by SARS-CoV-2 requires the binding between the receptor-binding domain of the viral spike protein and the cellular angiotensin-converting enzyme 2 (ACE2). Here, we briefly reviewed the mechanisms underlying the interaction between SARS-CoV-2 and ACE2, and summarized the latest research progress on SARS-CoV-2 neutralizing monoclonal antibodies and nanobodies, so as to better understand the development process and drug research direction of COVID-19. This review may facilitate understanding the development of neutralizing antibody drugs for emerging infectious diseases, especially for COVID-19.
Angiotensin-Converting Enzyme 2
;
Antibodies, Monoclonal
;
Antibodies, Neutralizing
;
Antibodies, Viral
;
COVID-19
;
Humans
;
Peptidyl-Dipeptidase A/metabolism*
;
Protein Binding
;
SARS-CoV-2
;
Single-Domain Antibodies
;
Spike Glycoprotein, Coronavirus/metabolism*
5.Effect of moxibustion with deqi on Aβ-receptor mediated transport and enzymatic degradation in hippocampus in rats with Alzheimer's disease.
Zhi-Mai LV ; Dan-Dan HUANG ; Ding-Yi XIE ; Rui-Zhen YUE ; Jin-Wei WANG ; Wei-Feng LUO ; Ri-Xin CHEN
Chinese Acupuncture & Moxibustion 2022;42(8):899-906
OBJECTIVE:
To observe the clinical effect of moxibustion with deqi on Alzheimer's disease (AD) rats, and evaluate its effect on β-amyloid (Aβ) transport and enzymatic degradation proteins, to explore its molecular mechanism for improving cognitive function.
METHODS:
Sixty SPF-grade male SD rats were randomly divided into a blank group (8 rats), a sham-operation group (8 rats) and a model establishment group (44 rats). The rats in the model establishment group were injected with Aβ1-42 at bilateral ventricles to establish AD model. Among the 38 rats with successful model establishment, 8 rats were randomly selected as the model group, and the remaining rats were treated with mild moxibustion at "Dazhui" (GV 14), once a day, 40 min each time, for 28 days. According to whether deqi appeared and the occurrence time of deqi, the rats were divided into a deqi group (12 rats), a delayed deqi group (10 rats) and a non-deqi group (8 rats). After the intervention, the Morris water maze test was applied to evaluate the cognitive function; the HE staining was applied to observe the brain morphology; the Western blot method was applied to measure the protein expression of Aβ and its receptor mediated transport [low-density lipoprotein receptor-related protein (LRP) 1, receptor for advanced glycation end products (RAGE), apolipoprotein E (ApoE)] and enzymatic degradation [neprilysin (NEP), insulin degrading enzyme (IDE), endothelin converting enzyme (ECE)-1 and angiotensin converting enzyme (ACE) 2].
RESULTS:
Compared with the sham-operation group, in the model group, the escape latency was prolonged (P<0.01), and the times of platform crossing and the ratio of platform quadrant to total time were reduced (P<0.01); the brain tissue was seriously damaged; the expression of hippocampal Aβ and RAGE was increased (P<0.01), and the expression of hippocampal LRP1, ApoE, NEP, IDE, ECE-1 and ACE2 was decreased (P<0.01). Compared with the model group, the escape latency was shortened in the deqi group (P<0.05, P<0.01), and the escape latency in the delayed deqi group and the non-deqi group was shortened from Day 2 to Day 5 (P<0.05, P<0.01), and the times of platform crossing and the ratio of platform quadrant to total time were increased in the deqi group and the delayed deqi group (P<0.01, P<0.05); the brain damage in each moxibustion group was reduced, which was smallest in the deqi group, followed by the delayed deqi group and the non-deqi group; the expression of Aβ and RAGE was decreased (P<0.01, P<0.05) and the expression of LRP1 and IDE was increased in each moxibustion group (P<0.01, P<0.05); the expression of ApoE was increased in the deqi group and the delayed deqi group (P<0.01, P<0.05); the expression of NEP was increased in deqi group (P<0.05), and the expression of ECE-1 and ACE2 was increased in the deqi group and the delayed deqi group (P<0.05). Compared with the delayed deqi group and the non-deqi group, the escape latency in the deqi group was shortened from Day 3 to Day 5 (P<0.05), and the times of platform crossing and the ratio of platform quadrant to total time were increased (P<0.05, P<0.01). Compared with the non-deqi group, the expression of Aβ was reduced (P<0.05), the expression of LRP1 and ApoE was increased in the deqi group (P<0.05). The expression of NEP in the deqi group was higher than that in the delayed deqi group and the non-deqi group (P<0.05).
CONCLUSION
Compared with non-deqi, moxibustion with deqi could promote Aβ transport and degradation, thereby reducing Aβ level in the brain and improving cognitive function for AD rats.
Alzheimer Disease/therapy*
;
Amyloid beta-Peptides/genetics*
;
Angiotensin-Converting Enzyme 2
;
Animals
;
Apolipoproteins E/metabolism*
;
Hippocampus/metabolism*
;
Male
;
Moxibustion
;
Rats
;
Rats, Sprague-Dawley
6.The bioactivity of angiotensin II and the effects of related Chinese Herbs.
China Journal of Chinese Materia Medica 2003;28(5):394-431
OBJECTIVETo review the bioactivity of angiotensin II and the effects of Chinese herbs on it.
METHODThe correlative documents published in recent years were summarized.
RESULTAngiotensin II plays an important role in the development of many diseases, such as hypertension, arteriosclerosis, myocardial lesion due to ischemia and reperfusion, cardiac hypertrophy and fibrosis, dysfunction of fibrinolytic system, thrombosis, renal failure etc. Some Chinese herbs inhibit the actions of angiotensin II.
CONCLUSIONFurther researches must be done to investigate the bioactivity of angiotensin II and the effects of Chinese herbs on preventing the body tissue from being impaired by it.
Angiotensin II ; metabolism ; physiology ; Angiotensin-Converting Enzyme Inhibitors ; pharmacology ; Animals ; Blood Pressure ; drug effects ; Cardiomegaly ; physiopathology ; Drugs, Chinese Herbal ; isolation & purification ; pharmacology ; Heart Failure ; physiopathology ; Humans ; Hypertension ; physiopathology ; Myocardial Reperfusion Injury ; physiopathology ; Plants, Medicinal ; chemistry ; Receptor, Angiotensin, Type 2 ; physiology
7.A Chinese Herb Prescription "Fang-gan Decoction" Protects Against Damage to Lung and Colon Epithelial Cells Caused by the SARS-CoV-2 Spike Protein by Regulating the TGF-β/Smad2/3 and NF-κB Pathways.
Chao HUANG ; Hao-Sheng LIU ; Bing-Jun LIANG ; Sheng-Rong LIAO ; Wei-Zeng SHEN
Chinese Medical Sciences Journal 2023;38(3):206-217
Objective To explore the effects and mechanisms of a traditional Chinese medicine (TCM) prescription, "Fang-gan Decoction" (FGD), in protecting against SARS-CoV-2 spike protein-induced lung and intestinal injuries in vitro and in vivo.Methods Female BALB/c mice and three cell lines pretreated with FGD were stimulated with recombinant SARS-CoV-2 spike protein (spike protein). Hematoxylin-eosin (HE) staining and pathologic scoring of tissues, cell permeability and viability, and angiotensin-converting enzyme 2 (ACE2) expression in the lung and colon were detected. Enzyme-linked immunosorbent assay (ELISA) was performed to detect the levels of inflammatory factors in serum and cell supernatant. The expression of NF-κB p65, p-NF-κB p65, p-IκBα, p-Smad2/3, TGF-β1, Caspase3, and Bcl-2 was evaluated by Western blotting.Results FGD protected against the damage to the lung and colon caused by the spike protein in vivo and in vitro according to the pathologic score and cell permeability and viability (P<0.05). FGD up-regulated ACE2 expression, which was reduced by the spike protein in the lung and colon, significantly improved the deregulation of inflammatory markers caused by the spike protein, and regulated the activity of TGF-β/Smads and NF-κB signaling.Conclusion Traditional Chinese medicine has a protective effect on lung and intestinal tissue injury stimulated by the spike protein through possible regulatory functions of the NF-κB and TGF-β1/Smad pathways with tissue type specificity.
Mice
;
Animals
;
Female
;
Humans
;
NF-kappa B/metabolism*
;
Spike Glycoprotein, Coronavirus/pharmacology*
;
Transforming Growth Factor beta1/metabolism*
;
Angiotensin-Converting Enzyme 2/pharmacology*
;
COVID-19
;
SARS-CoV-2/metabolism*
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Lung
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Antineoplastic Agents
;
Transforming Growth Factor beta/pharmacology*
;
Epithelial Cells/metabolism*
;
Colon
8.Angiotensin converting enzyme 2 alleviates infectious bronchitis virus-induced cellular inflammation by suppressing IL-6/JAK2/STAT3 signaling pathway.
Xiaoxia JI ; Huanhuan WANG ; Chang MA ; Zhiqiang LI ; Xinyu DU ; Yuanshu ZHANG
Chinese Journal of Biotechnology 2023;39(7):2669-2683
The goal of this study was to investigate the regulatory effect of angiotensin converting enzyme 2 (ACE2) on cellular inflammation caused by avian infectious bronchitis virus (IBV) and the underlying mechanism of such effect. Vero and DF-1 cells were used as test target to be exposed to recombinant IBV virus (IBV-3ab-Luc). Four different groups were tested: the control group, the infection group[IBV-3ab-Luc, MOI (multiplicity of infection)=1], the ACE2 overexpression group[IBV-3ab Luc+pcDNA3.1(+)-ACE2], and the ACE2-depleted group (IBV-3ab-Luc+siRNA-ACE2). After the cells in the infection group started to show cytopathic indicators, the overall protein and RNA in cell of each group were extracted. real-time quantitative polymerase chain reaction (RT-qPCR) was used to determine the mRNA expression level of the IBV nucleoprotein (IBV-N), glycoprotein 130 (gp130) and cellular interleukin-6 (IL-6). Enzyme linked immunosorbent assay (ELISA) was used to determine the level of IL-6 in cell supernatant. Western blotting was performed to determine the level of ACE2 phosphorylation of janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3). We found that ACE2 was successfully overexpressed and depleted in both Vero and DF-1 cells. Secondly, cytopathic indicators were observed in infected Vero cells including rounding, detaching, clumping, and formation of syncytia. These indicators were alleviated in ACE2 overexpression group but exacerbated when ACE2 was depleted. Thirdly, in the infection group, capering with the control group, the expression level of IBV-N, gp130, IL-6 mRNA and increased significantly (P < 0.05), the IL-6 level was significant or extremely significant elevated in cell supernatant (P < 0.05 or P < 0.01); the expression of ACE2 decreased significantly (P < 0.05); protein phosphorylation level of JAK2 and STAT3 increased significantly (P < 0.05). Fourthly, comparing with the infected group, the level of IBV-N mRNA expression in the ACE2 overexpression group had no notable change (P > 0.05), but the expression of gp130 mRNA, IL-6 level and expression of mRNA were elevated (P < 0.05) and the protein phosphorylation level of JAK2 and STAT3 decreased significantly (P < 0.05). In the ACE2-depleted group, there was no notable change in IBV-N (P > 0.05), but the IL-6 level and expression of mRNA increased significantly (P < 0.05) and the phosphorylation level of JAK2 and STAT3 protein decreased slightly (P > 0.05). The results demonstrated for the first time that ACE2 did not affect the replication of IBV in DF-1 cell, but it did contribute to the prevention of the activation of the IL-6/JAK2/STAT3 signaling pathway, resulting in an alleviation of IBV-induced cellular inflammation in Vero and DF-1 cells.
Animals
;
Chlorocebus aethiops
;
Humans
;
Interleukin-6/genetics*
;
Janus Kinase 2/pharmacology*
;
Infectious bronchitis virus/metabolism*
;
STAT3 Transcription Factor/metabolism*
;
Angiotensin-Converting Enzyme 2/pharmacology*
;
Cytokine Receptor gp130/metabolism*
;
Vero Cells
;
Signal Transduction
;
Inflammation
;
RNA, Messenger
9.Effects of enalapril on plasma Ang II level and the expression of AT1 in blood vessel and kidney of type 2 diabetic rats.
Jian YANG ; Chun XUE ; Gang HU
Acta Pharmaceutica Sinica 2005;40(3):208-212
AIMTo study the plasma angiotensin II (Ang II) levels and the expressions of angiotensin II1 receptor (AT1) in blood vessels and kidneys in diabetic and high fat diet rats, and the effects of enalapril on plasma Ang II levels and the expressions of AT1 in blood vessels and kidneys in diabetic rats.
METHODSThe plasma Ang II level was assayed with 125I-Ang II radioimmunoassay, and the expression of AT1 in blood vessel and kidney was analyzed with immunohistochemical technique.
RESULTSThe plasma Ang II level was significantly higher in type 2 diabetic rats (241 +/- 49) pg x mL(-1) than that in the control (71 +/- 22) pg x mL , high fat diet group (151 +/- 29) pg x mL(-1) (P < 0.01) , and enalapril-treated groups (136 +/- 25) pg x mL(-1) (P < 0.05). The plasma Ang II levels in high fat diet and in enalapril-treated groups were also significantly higher than that in control group ( P < 0.01 ). With immunohistochemical technique, it was found that the expression of AT1 in endothelial cells of blood vessels, vascular smooth muscle cells, and kidneys in diabetic group increased. The expression of AT1 in endothelial cells of blood vessels, vascular smooth muscle cells, and kidney in enalapril-treated group was similar to that in control group.
CONCLUSIONThe plasma Ang II levels and the expression of AT1 in type 2 diabetic and high fat diet rats increased. Enalapril was shown to decrease the plasma Ang II level and downregulate the expression of AT1 in blood vessels and kidneys in type 2 diabetic rats.
Angiotensin II ; blood ; Angiotensin-Converting Enzyme Inhibitors ; pharmacology ; Animals ; Blood Vessels ; cytology ; metabolism ; Diabetes Mellitus, Type 2 ; blood ; metabolism ; Dietary Fats ; administration & dosage ; Enalapril ; pharmacology ; Endothelial Cells ; metabolism ; Kidney ; metabolism ; Male ; Myocytes, Smooth Muscle ; metabolism ; Rats ; Rats, Sprague-Dawley ; Receptor, Angiotensin, Type 1 ; metabolism
10.The effects of ACEI on calpain-mediated cardiomyocytes apoptosis and cardiac function in diabetic rats.
Xiao-Xiao QIU ; Jian-Min LI ; Jing ZHAO ; Xian-Feng LIN ; Shuai LOU ; Ke-Ke JIN ; Xian-Zhong JIANG
Chinese Journal of Applied Physiology 2013;29(4):359-362
OBJECTIVETo investigate the effects of angiotensin converting enzyme inhibitor (ACEI) captopril on Calpain-mediated cardiomyocytes apoptosis and cardiac function in diabetic rats.
METHODSThirty adult male SD rats were randomly divided into 3 groups (n = 10), normal control group (NC group), diabetes mellitus group (DM group)and captopril treated group (Cap group). Streptozocin (STZ) were used to make the model of diabetes mellitus, captopril was administrated by gavage at the dose of 50 mg/kg every day, while in NC group and DM group the same volume of normal saline was administrated. Twelve weeks later, left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVDEP), maximal rise rate of left ventricular pressure (+ dp/dtmax) and maximal fall rate of left ventricular pressure (- dp/dtmax) were detected; Western blot was used to detect the expression of Calpain-1 Calpain-2, Bcl-2, Bax and total Caspase3 protein; apoptosis index (AI) were assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL).
RESULTSCompared with NC group, LVDEP was significantly higher; LVSP, + dp/dtmax and - dp/dtmax were significantly decreased (P < 0.05); Bcl-2 protein expression was decreased; the expression of Calpain-1, Calpain-2, Bax and total Caspase3 protein were increased; the value of AI was significantly increased. Compared with DM group, LVDEP was significantly lower; LVSP, + dp/dtmax and - dp/dtmax were significantly increased (P < 0.05); Bcl-2 protein expression was increased, the expression of Calpain-1, Calpain-2, Bax and total Caspase3 protein were decreased; the value of AI was significantly decreased (P < 0.05).
CONCLUSIONCaptopril can protect diabetic myocardial structure through inhibiting activation of Calpain-1 and Calpain-2, up-regulating the expression of Bcl-2, down-regulating the expression of Bax to inhibit Caspase3 dependent apoptosis, thereby improving the ventricular function and myocardial structure.
Angiotensin-Converting Enzyme Inhibitors ; pharmacology ; Animals ; Apoptosis ; drug effects ; Calpain ; metabolism ; Cardiomyopathies ; pathology ; Caspase 3 ; metabolism ; Diabetes Mellitus, Experimental ; metabolism ; pathology ; physiopathology ; Male ; Myocytes, Cardiac ; cytology ; drug effects ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Rats ; Rats, Sprague-Dawley ; bcl-2-Associated X Protein ; metabolism