Implications of ADAM17 activation for hyperglycaemia, obesity and type 2 diabetes

Matthews, Jennifer; Villescas, Sofia; Herat, Lakshini Y.; Schlaich, Markus P.; Matthews, Vance B.

doi:10.1042/bsr20210029

Cited by 14 publications

(14 citation statements)

References 80 publications

(116 reference statements)

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“…Maximal ADAM1 7 expression in PBCs of COVID-19 patients with obesity (BMI > 30) is explicable, considering that obesity often associates with metabolic inflammation, with which ADAM17 activity has recognized links, through proteolytic processing of pro-TNFalfa, ACE2, IL-6R and other membrane-anchored proteins in adipose tissue and other tissues [ 45 , 46 ]. Evidence in humans and rodents indicates that aging and obesity cooperatively increase vascular endothelial ADAM17 activity and the release of soluble TNFalfa by adipose tissue cells [ 47 ].…”

Section: Discussionmentioning

confidence: 99%

Increased mRNA Levels of ADAM17, IFITM3, and IFNE in Peripheral Blood Cells Are Present in Patients with Obesity and May Predict Severe COVID-19 Evolution

et al. 2022

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Gene expression patterns in blood cells from SARS-CoV-2 infected individuals with different clinical phenotypes and body mass index (BMI) could help to identify possible early prognosis factors for COVID-19. We recruited patients with COVID-19 admitted in Hospital Universitari Son Espases (HUSE) between March 2020 and November 2021, and control subjects. Peripheral blood cells (PBCs) and plasma samples were obtained on hospital admission. Gene expression of candidate transcriptomic biomarkers in PBCs were compared based on the patients’ clinical status (mild, severe and critical) and BMI range (normal weight, overweight, and obesity). mRNA levels of ADAM17, IFITM3, IL6, CXCL10, CXCL11, IFNG and TYK2 were increased in PBCs of COVID-19 patients (n = 73) compared with controls (n = 47), independently of sex. Increased expression of IFNE was observed in the male patients only. PBC mRNA levels of ADAM17, IFITM3, CXCL11, and CCR2 were higher in those patients that experienced a more serious evolution during hospitalization. ADAM17, IFITM3, IL6 and IFNE were more highly expressed in PBCs of patients with obesity. Interestingly, the expression pattern of ADAM17, IFITM3 and IFNE in PBCs was related to both the severity of COVID-19 evolution and obesity status, especially in the male patients. In conclusion, gene expression in PBCs can be useful for the prognosis of COVID-19 evolution.

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Section: Discussionmentioning

confidence: 99%

Increased mRNA Levels of ADAM17, IFITM3, and IFNE in Peripheral Blood Cells Are Present in Patients with Obesity and May Predict Severe COVID-19 Evolution

et al. 2022

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“…This finding would be explained by two different approaches previously proposed in the literature. One would be the influence of high blood glucose levels in inducing hyperactivation of the sympathetic nervous system and also promoting ADAM17 expression [ 18 ]. Matthews et al hypothesized that an increase in ADAM17 induces renal sympathetic nervous system activity and in turn induces SGLT2 (Sodium Glucose Cotransporter 2) expression, which promotes glucose reabsorption and hyperglycemia [ 18 ].…”

Section: Discussionmentioning

confidence: 99%

“…One would be the influence of high blood glucose levels in inducing hyperactivation of the sympathetic nervous system and also promoting ADAM17 expression [ 18 ]. Matthews et al hypothesized that an increase in ADAM17 induces renal sympathetic nervous system activity and in turn induces SGLT2 (Sodium Glucose Cotransporter 2) expression, which promotes glucose reabsorption and hyperglycemia [ 18 ]. In this line, our study demonstrated that Adam17 deletion on proximal tubular cells prevents increased blood glucose levels and glucose intolerance to a lesser extent.…”

Section: Discussionmentioning

confidence: 99%

Redefining the Role of ADAM17 in Renal Proximal Tubular Cells and Its Implications in an Obese Mouse Model of Pre-Diabetes

Palau

Villanueva

Jarrín

et al. 2021

IJMS

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Acute and chronic kidney lesions induce an increase in A Disintegrin And Metalloproteinase domain 17 (ADAM17) that cleaves several transmembrane proteins related to inflammatory and fibrotic pathways. Our group has demonstrated that renal ADAM17 is upregulated in diabetic mice and its inhibition decreases renal inflammation and fibrosis. The purpose of the present study was to analyze how Adam17 deletion in proximal tubules affects different renal structures in an obese mice model. Tubular Adam17 knockout male mice and their controls were fed a high-fat diet (HFD) for 22 weeks. Glucose tolerance, urinary albumin-to-creatinine ratio, renal histology, and pro-inflammatory and pro-fibrotic markers were evaluated. Results showed that wild-type mice fed an HFD became obese with glucose intolerance and renal histological alterations mimicking a pre-diabetic condition; consequently, greater glomerular size and mesangial expansion were observed. Adam17 tubular deletion improved glucose tolerance and protected animals against glomerular injury and prevented podocyte loss in HFD mice. In addition, HFD mice showed more glomerular macrophages and collagen accumulation, which was prevented by Adam17 deletion. Galectin-3 expression increased in the proximal tubules and glomeruli of HFD mice and ameliorated with Adam17 deletion. In conclusion, Adam17 in proximal tubules influences glucose tolerance and participates in the kidney injury in an obese pre-diabetic murine model. The role of ADAM17 in the tubule impacts on glomerular inflammation and fibrosis.

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“… 49 Furthermore, evidence is provided that ADAM-17 plays a role in metabolic syndrome-related pathologies. 50 , 51 On the other hand, some clear data also show the possible relationship between the presence of metabolic syndrome and the severity of COVID-19. 52 Accordingly, several of the features of the metabolic syndrome seem to be associated with a worse prognosis in patients with COVID-19.…”

Section: Risk Factors For Covid-19 and Defective Efferocytosismentioning

confidence: 99%

Importance of Efferocytosis in COVID-19 Mortality

Erol¹

2022

IDR

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COVID-19 is a generally benign coronavirus disease that can spread rapidly, except for those with a group of risk factors. Since the pathogenesis responsible for the severity of the disease has not been clearly revealed, effective treatment alternatives has not been developed. The hallmark of the SARS-CoV-2-infected cells is apoptosis. Apoptotic cells are cleared through a sterile process defined as efferocytosis by professional and nonprofessional phagocytic cells. The disease would be rapidly brought under control in the organism that can achieve effective efferocytosis, which is also a kind of innate immune response. In the risk group, the efferocytic process is defective. With the addition of the apoptotic cell load associated with SARS-COV-2 infection, failure to achieve efferocytosis of dying cells can initiate secondary necrosis, which is a highly destructive process. Uncontrolled inflammation and coagulation abnormalities caused by secondary necrosis reason in various organ failures, lung in particular, which are responsible for the poor prognosis. Following the short and simplified information, this opinion paper aims to present possible treatment options that can control the severity of COVID-19 by detailing the mechanisms that can cause defective efferocytosis.

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Implications of ADAM17 activation for hyperglycaemia, obesity and type 2 diabetes

Cited by 14 publications

References 80 publications

Increased mRNA Levels of ADAM17, IFITM3, and IFNE in Peripheral Blood Cells Are Present in Patients with Obesity and May Predict Severe COVID-19 Evolution

Increased mRNA Levels of ADAM17, IFITM3, and IFNE in Peripheral Blood Cells Are Present in Patients with Obesity and May Predict Severe COVID-19 Evolution

Redefining the Role of ADAM17 in Renal Proximal Tubular Cells and Its Implications in an Obese Mouse Model of Pre-Diabetes

Importance of Efferocytosis in COVID-19 Mortality

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