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

Autor: Vanesa Palau, Sofia Villanueva, Josué Jarrín, David Benito, Eva Márquez, Eva Rodríguez, María José Soler, Anna Oliveras, Javier Gimeno, Laia Sans, Marta Crespo, Julio Pascual, Clara Barrios, Marta Riera
Přispěvatelé: Institut Català de la Salut, [Palau V, Villanueva S, Jarrín J, Benito D, Márquez E, Rodríguez E] Department of Nephrology, Hospital del Mar-Institut Hospital del Mar d’Investigacions Mèdiques (IMIM), 08003 Barcelona, Spain. [Soler MJ] Grup de Recerca en Nefrologia, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Servei de Nefrologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain, Vall d'Hebron Barcelona Hospital Campus
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Urogenital System::Urinary Tract::Kidney::Nephrons::Kidney Tubules::Kidney Tubules
Proximal [ANATOMY]
QH301-705.5
Galectin 3
Mice
Obese
ADAM17 Protein
Diet
High-Fat
enfermedades nutricionales y metabólicas::enfermedades metabólicas::trastornos del metabolismo de la glucosa::diabetes mellitus::estado prediabético [ENFERMEDADES]
Catalysis
Article
Inorganic Chemistry
Kidney Tubules
Proximal
Prediabetic State
Gene Knockout Techniques
Mice
Sodium-Glucose Transporter 2
Animals
Ratolins
Obesity
Physical and Theoretical Chemistry
Biology (General)
Eukaryota::Animals::Chordata::Vertebrates::Mammals::Eutheria::Rodentia::Muridae::Murinae::Mice [ORGANISMS]
Molecular Biology
QD1-999
Spectroscopy
ADAM17
Diabetis
sistema urogenital::sistema urinario::riñón::nefronas::túbulos renales::túbulos renales proximales [ANATOMÍA]
Organic Chemistry
obesity
pre-diabetes
renal proximal tubular cells
Ronyons - Malalties
General Medicine
Glucose Tolerance Test
Computer Science Applications
Disease Models
Animal
Chemistry
Case-Control Studies
Nutritional and Metabolic Diseases::Metabolic Diseases::Glucose Metabolism Disorders::Diabetes Mellitus::Prediabetic State [DISEASES]
Collagen
Pre-diabetes
Renal proximal tubular cells
Eukaryota::animales::Chordata::vertebrados::mamíferos::Eutheria::Rodentia::Muridae::Murinae::ratones [ORGANISMOS]
Zdroj: International Journal of Molecular Sciences; Volume 22; Issue 23; Pages: 13093
International Journal of Molecular Sciences, Vol 22, Iss 13093, p 13093 (2021)
International Journal of Molecular Sciences
Scientia
ISSN: 1422-0067
DOI: 10.3390/ijms222313093
Popis: ADAM17; Obesidad; Células tubulares proximales renales ADAM17; Obesity; Renal proximal tubular cells ADAM17; Obesitat; Cèl·lules tubulars proximals renals 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. This research was funded by ISCIIII-FEDER grant numbers PI16/00620 and PI17/00257; ISCIII-RETICS REDinREN RD16/0009/0013, and ISCIII-RICORS RD21/0005. C.B. is also funded by the Catalan Health Department (Generalitat de Catalunya) contract PERIS STL008/18/00018 to develop clinical and epidemiological studies mainly focused on diabetes and its associations with new biomarkers. V.P. is a research fellow of ISCIII-FSE project FI17/00025.
Databáze: OpenAIRE
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