ADAM17

ADAM metallopeptidase domain 17

Gene Context Sentence


Table 2. Analysis of context sentence of ADAM17 gene in 29 abstracts.

PMID Gene Context Sentence
32354022 ACE2 can be shed by two proteases, ADAM17 and TMPRSS2. […] TMPRSS2-cleaved ACE2 allows SARS-CoV-2 cell entry, whereas ADAM17-cleaved ACE2 offers protection to organs.
32423094 Other genes, out from the RAS-pathway, might directly or indirectly impact on the ACE1/ACE2 balance by influencing its main actors (e.g., ABO locus, SRY, SOX3, ADAM17).
32664949 TMPRSS2, ADAM17, tissue inhibitor of metalloproteinase (TIMP)3, angiotensinogen (AGT), transformation growth factor beta (TGFB1), connective tissue growth factor (CTGF), vascular endothelial growth factor (VEGF) A and fibronectin (FN) were interacted with ACE2, and the mRNA and protein of these molecules were expressed in lung epithelial cells.
32675206 Additional host molecules including ADAM17, cathepsin L, CD147 and GRP78 may also function as receptors for SARS-CoV-2.
32757420 We therefore performed data mining of two independent NCBI GEO genome-wide RNA expression files (GSE7894 and GSE994) and report that in both data sets, current smokers and never smokers have, on average, closely similar bronchial epithelial cell mRNA levels of ACE2, as well as TMPRSS2, coding for a serine protease priming SARS-Cov-2 for cell entry, and ADAM17, coding for a protease implicated in ACE2 membrane shedding.
32769398 A disintegrin and metalloproteinase 17 (ADAM17), an ectodomain sheddase, is a key component of ACE2 modulation and plays a complex role in inflammation and immunosurveillance. […] Much remains unknown regarding the immunopathogenesis of COVID-19, including how the virus affects ADAM17 expression, activity, and regulation. […] Three electronic databases (MEDLINE through PubMed, Embase through Ovid, and Google Scholar) were searched to identify articles relevant to ADAM17 and severe acute respiratory syndrome coronavirus 1 and 2. […] Infection with SARS-CoV-2 may lead to an increase in ADAM17 sheddase activity contributing to an exuberant macrophage-predominant inflammatory response and diminished immunosurveillance capacity for viral clearance. […] This clinical picture is consistent with dysregulation of many of the molecular pathways in which ADAM17 participates. […] Elucidation of the role of ADAM17 in COVID-19 may identify novel molecular targets for drug development and therapeutic repurposement.
32783758 It illustrates new analyses of the structure of ACE2 that provides better understanding of its actions particularly in lung and gut, shedding of ACE2 by ADAM17 (a disintegrin and metallopeptidase domain 17 protein), and role of TMPRSS2 (transmembrane serine proteases 2) in severe acute respiratory syndrome coronavirus-2 entry into host cells.
32784802 The entry process involves priming of the S protein by TMPRSS2 and ADAM17, which collectively mediate the binding and promote ACE2 shedding. […] In this study, microarray and RNA-sequencing (RNA-seq) expression data were utilized to profile the expression pattern of ACE2, ADAM17, and TMPRSS2 in type 2 diabetic (T2D) and non-diabetic human pancreatic islets. […] Islets from female donors showed higher ACE2 expression compared to males; the expression of ADAM17 and TMPRSS2 was not affected by gender. […] Obese (BMI > 30) donors have significantly higher expression levels of ADAM17 and TMPRSS2 relative to those from non-obese donors (BMI < 25). […] TMPRSS2 expression correlated positively with HbA1c and negatively with age, while ADAM17 and TMPRSS2 correlated positively with BMI.
32822911 We discuss that the metallopeptidase enzyme ADAM17, also known as tumor necrosis factor-α-converting enzyme, TACE, is responsible for shedding of angiotensin-converting enzyme 2 and membrane-bound interleukin (IL)-6 receptor. […] We argue that cytokine balance may be restored by recovering an IL-6 trans-signaling neutralizing buffer system through the mediation of recombinant soluble glycoprotein 130 and recombinant ADAM17/TACE prodomain inhibitor.
32844538 A1AT inhibits SARS-CoV-2 infection and two of the most important proteases in the pathophysiology of Covid-19: the transmembrane serine protease 2 (TMPRSS2) and the disintegrin and metalloproteinase 17 (ADAM17). […] ADAM17 mediates ACE2, IL-6R, and TNF-α shedding. […] In this review, we focused on the interplay between A1AT with TMPRSS2, ADAM17 and immune molecules, and the role of A1AT in the pathophysiology of Covid-19, opening new avenues for investigating effective treatments.
32867008 Additionally, the presence of resolvins and the desintegrin metalloprotease ADAM17 provide a putative protection to the skin, explaining the majority of COVID-19 manifestations to be extra cutaneous.
32966970 ACE2 is cleaved from the cells by metalloproteases ADAM10 and ADAM17.
33017914 ALA reduces ADAM17 activity and ACE2 upregulation.
33110240 We discussed a possible link between the activation of hypoxia inducible factor 1α (HIF-1α) and cell entry of SARS-CoV-2, since HIF-1α is shown to suppress the angiotensin-converting enzyme 2 (ACE2) receptor and transmembrane protease serine 2 (TMPRSS2) and upregulate disintegrin and metalloproteinase domain-containing protein 17 (ADAM17).
33117379 Therefore, the occurrence of specific comorbidities associated with renin-angiotensin system (RAS) imbalance mediated by the interaction between angiotensin-converting enzyme 2 (ACE2) and desintegrin and metalloproteinase domain 17 (ADAM17), along with specific genetic factors mainly associated with type II transmembrane serine protease (TMPRSS2) expression, could be decisive for the clinical outcome of COVID-19. […] Indeed, the exacerbated ADAM17-mediated ACE2, TNF-α, and IL-6R secretion emerges as a possible underlying mechanism for the acute inflammatory immune response and the activation of the coagulation cascade. […] Therefore, in this review, we focus on the main pathophysiological aspects of ACE2, ADAM17, and TMPRSS2 host proteins in COVID-19. […] Additionally, we discuss a possible mechanism to explain the deleterious effect of ADAM17 and TMPRSS2 over-activation in the COVID-19 outcome.
33126657 The importance of ACE2 shedding, associated with the release of soluble ACE2 and ADAM17-mediated activation of tumor necrosis factor-α (TNF-α)-signaling is unclear.
33153216 The expression of apparatus mediating SARS-CoV-2 entry, including angiotensin-converting enzyme 2, transmembrane protease serine 2 (TMPRSS2) and a disintegrin and metalloprotease 17 (ADAM17), within the renal tubular cells is highly associated with acute kidney injury mediated by SARS-CoV-2.
33199671 We also identified miRNAs that bind to receptor proteins, such as ACE2, ADAM17, and TMPRSS2, which are important for understanding the infection mechanism of SARS-CoV-2.
33239231 Third, AAT has potent anti-inflammatory properties, in part through inhibiting both nuclear factor-kappa B (NFκB) activation and ADAM17 (also known as tumor necrosis factor-alpha converting enzyme), and thus may dampen the hyper-inflammatory response of COVID-19. […] AAT inhibition of ADAM17 also prevents shedding of ACE2 and hence may preserve ACE2 inhibition of bradykinin, reducing the ability of bradykinin to cause a capillary leak in COVID-19.
33243116 In this report, we focus on the role of host cell proteases (ACE2, ADAM17, TMPRSS2) and androgen receptor (AR) in SARS-CoV-2 infection. […] The hypotheses put forth by us are based on the role played by the proteases ACE2, ADAM17, TMPRSS2 and AR in SARS-CoV-2 infection which were deduced based on various studies.
33251580 Because epicardial adipose tissue (EAT) expresses ACE2, we wanted to identify the main factors associated with ACE2 levels and its cleavage enzyme, ADAM17, in epicardial fat. […] From 36 patients, biopsies were used for RNA expression analysis by real-time PCR of ACE1, ACE2 and ADAM17. […] Epicardial fat biopsies expressed higher levels of ACE2 (1.53 [1.49-1.61] vs 1.51 [1.47-1.56] a.u., P < .05) and lower ADAM17 than subcutaneous fat (1.67 [1.65-1.70] vs 1.70 [1.66-1.74] a.u., P < .001). […] Both genes were increased in epicardial fat from patients with type 2 diabetes mellitus (T2DM) (1.62 [1.50-2.28] vs 1.52 [1.49-1.55] a.u., P = .05 for ACE2 and 1.68 [1.66-1.78] vs 1.66 [1.63-1.69] a.u., P < .05 for ADAM17).
33275517 Loss of membrane ACE2 and a corresponding increase in plasma ACE2 are associated with worsened cardiovascular disease outcomes, a mechanism attributed to a disintegrin and metalloproteinase (ADAM17). […] SARS-CoV-2 infection also leads to ADAM17 activation, a positive feedback cycle that exacerbates ACE2 loss. […] Therefore, the relationship between cardiovascular disease and COVID-19 is critically dependent on the loss of membrane ACE2 by ADAM17-mediated proteolytic cleavage.
33357215 The PtdSer exposure may be an important mechanism related to ADAM17-mediated ACE2, TNF-α, EGFR and IL-6R shedding, and the activation of TF on the surface of infected endothelial cells.
33399851 SARS-CoV-2 can decrease cell surface ACE2 directly by internalization of ACE2 bound to the virus and indirectly by increased ADAM17 (a disintegrin and metalloproteinase 17)-mediated shedding of ACE2.
33419885 IAV also increased the expression of two proteases known to cleave ACE2, sheddase ADAM17 (TACE) and TMPRSS2 and increased the TMPRSS2 zymogen and its mature fragments, implicating proteolytic autoactivation.
33426683 Other important proteins involved in this process include disintegrin and metalloproteinase domain-containing protein 17 (ADAM17) also known as tumour necrosis factor-α-converting enzyme and transmembrane serine protease 2. […] Membrane-bound ACE2 ectodomain shedding is mediated by ADAM17 upon viral spike binding, Ang II overproduction and in several diseases.
33479758 Treatment with viral spike protein induced a decrease in full-length (i.e. transmembrane) ACE2, an increase in levels of a short intracellular ACE2 polypeptide and an increase in ADAM17 activity in cells, together with an increase in levels of soluble ACE2 and major proinflammatory cytokines in the culture medium. […] Furthermore, possible up-regulation of viral entry by the drug-induced increase in expression of transmembrane ACE2 is counteracted by additional mechanisms, particularly by drug-induced inhibition of ADAM17 activity.
33531686 This Comment explores the interaction between COVID-19 and cancer with attention paid to the modulation by cancer treatments of both ADAM17 and TMPRSS2, the proteases which control ACE2 processing, the SARS-CoV-2 target.
33584343 Virion binding to ACE2 for host cell entry leads to internalization of both via endocytosis, as well as activation of ADAM17/TACE, resulting in downregulation of ACE2 and loss of its protective actions in the lungs and other organs.