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Article

Both Specific Endothelial and Proximal Tubular Adam17 Deletion Protect against Diabetic Nephropathy

1
Department of Nephrology, Hospital del Mar-Institut Hospital del Mar d’Investigacions Mèdiques, 08003 Barcelona, Spain
2
Institute for Regenerative Medicine (IREM), Faculty of Medicine, University of Zurich, 8952 Schlieren, Switzerland
3
Institute of Parasitology, Vetsuisse Faculty and Faculty of Medicine, University of Zurich, CH-8057 Zurich, Switzerland
4
Department of Cardiovascular Surgery, Charité Universitätsmedizin Berlin, 10117 Berlin, Germany
5
German Heart Center Berlin, Department of Cardiothoracic and Vascular Surgery, 13353 Berlin, Germany
*
Authors to whom correspondence should be addressed.
Current location: Bioscience Cardiovascular, Research and Early Development, Cardiovascular, Renal and Metabolism, R&D BioPharmaceuticals, AstraZeneca, 431 50 Gothenburg, Sweden.
Current location: Nephrology Research Group, Vall d’Hebron Research Institute (VHIR), Nephrology Deparment, Hospital Universitari Vall d’Hebron, Univeristat Autònoma de Barcelona, 08035 Barcelona, Spain.
Academic Editor: Georgina Hotter
Int. J. Mol. Sci. 2021, 22(11), 5520; https://doi.org/10.3390/ijms22115520
Received: 21 April 2021 / Revised: 17 May 2021 / Accepted: 19 May 2021 / Published: 24 May 2021
ADAM17 is a disintegrin and metalloproteinase capable of cleaving the ectodomains of a diverse variety of molecules including TNF-α, TGF-α, L-selectin, and ACE2. We have previously demonstrated that renal ADAM17 is upregulated in diabetic mice. The role of endothelial (eAdam17) and proximal tubular (tAdam17) Adam17 deletion in renal histology, modulation of the renin angiotensin system (RAS), renal inflammation, and fibrosis was studied in a mouse model of type 1 Diabetes Mellitus. Moreover, the effect of Adam17 deletion in an in vitro 3D cell culture from human proximal tubular cells under high glucose conditions was evaluated. eAdam17 deletion attenuates renal fibrosis and inflammation, whereas tAdam17 deletion decreases podocyte loss, attenuates the RAS, and decreases macrophage infiltration, α-SMA and collagen accumulation. The 3D in vitro cell culture reinforced the findings obtained in tAdam17KO mice with decreased fibrosis in the Adam17 knockout spheroids. In conclusion, Adam17 deletion either in the endothelial or the tubular cells mitigates kidney injury in the diabetic mice by targeting different pathways. The manipulation of Adam17 should be considered as a therapeutic strategy for treating DN. View Full-Text
Keywords: ADAM17; diabetic nephropathy; endothelial deletion; renal proximal tubular deletion; 3D proximal tubular spheroids ADAM17; diabetic nephropathy; endothelial deletion; renal proximal tubular deletion; 3D proximal tubular spheroids
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MDPI and ACS Style

Palau, V.; Nugraha, B.; Benito, D.; Pascual, J.; Emmert, M.Y.; Hoerstrup, S.P.; Riera, M.; Soler, M.J. Both Specific Endothelial and Proximal Tubular Adam17 Deletion Protect against Diabetic Nephropathy. Int. J. Mol. Sci. 2021, 22, 5520. https://doi.org/10.3390/ijms22115520

AMA Style

Palau V, Nugraha B, Benito D, Pascual J, Emmert MY, Hoerstrup SP, Riera M, Soler MJ. Both Specific Endothelial and Proximal Tubular Adam17 Deletion Protect against Diabetic Nephropathy. International Journal of Molecular Sciences. 2021; 22(11):5520. https://doi.org/10.3390/ijms22115520

Chicago/Turabian Style

Palau, Vanesa, Bramasta Nugraha, David Benito, Julio Pascual, Maximilian Y. Emmert, Simon P. Hoerstrup, Marta Riera, and Maria J. Soler. 2021. "Both Specific Endothelial and Proximal Tubular Adam17 Deletion Protect against Diabetic Nephropathy" International Journal of Molecular Sciences 22, no. 11: 5520. https://doi.org/10.3390/ijms22115520

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