{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:47:36Z","timestamp":1787028456583,"version":"build-2736575974"},"reference-count":45,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,5,24]],"date-time":"2021-05-24T00:00:00Z","timestamp":1621814400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI14\/00557"],"award-info":[{"award-number":["PI14\/00557"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI17\/00257"],"award-info":[{"award-number":["PI17\/00257"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["RD16\/0009\/0013"],"award-info":[{"award-number":["RD16\/0009\/0013"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>ADAM17 is a disintegrin and metalloproteinase capable of cleaving the ectodomains of a diverse variety of molecules including TNF-\u03b1, TGF-\u03b1, 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, \u03b1-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.<\/jats:p>","DOI":"10.3390\/ijms22115520","type":"journal-article","created":{"date-parts":[[2021,5,24]],"date-time":"2021-05-24T12:38:01Z","timestamp":1621859881000},"page":"5520","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Both Specific Endothelial and Proximal Tubular Adam17 Deletion Protect against Diabetic Nephropathy"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3210-7924","authenticated-orcid":false,"given":"Vanesa","family":"Palau","sequence":"first","affiliation":[{"name":"Department of Nephrology, Hospital del Mar-Institut Hospital del Mar d\u2019Investigacions M\u00e8diques, 08003 Barcelona, Spain"},{"name":"Institute for Regenerative Medicine (IREM), Faculty of Medicine, University of Zurich, 8952 Schlieren, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0799-1594","authenticated-orcid":false,"given":"Bramasta","family":"Nugraha","sequence":"additional","affiliation":[{"name":"Institute of Parasitology, Vetsuisse Faculty and Faculty of Medicine, University of Zurich, CH-8057 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Benito","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Hospital del Mar-Institut Hospital del Mar d\u2019Investigacions M\u00e8diques, 08003 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4735-7838","authenticated-orcid":false,"given":"Julio","family":"Pascual","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Hospital del Mar-Institut Hospital del Mar d\u2019Investigacions M\u00e8diques, 08003 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maximilian Y.","family":"Emmert","sequence":"additional","affiliation":[{"name":"Institute for Regenerative Medicine (IREM), Faculty of Medicine, University of Zurich, 8952 Schlieren, Switzerland"},{"name":"Department of Cardiovascular Surgery, Charit\u00e9 Universit\u00e4tsmedizin Berlin, 10117 Berlin, Germany"},{"name":"German Heart Center Berlin, Department of Cardiothoracic and Vascular Surgery, 13353 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon P.","family":"Hoerstrup","sequence":"additional","affiliation":[{"name":"Institute for Regenerative Medicine (IREM), Faculty of Medicine, University of Zurich, 8952 Schlieren, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4362-7965","authenticated-orcid":false,"given":"Marta","family":"Riera","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Hospital del Mar-Institut Hospital del Mar d\u2019Investigacions M\u00e8diques, 08003 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3621-0766","authenticated-orcid":false,"given":"Maria Jos\u00e9","family":"Soler","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Hospital del Mar-Institut Hospital del Mar d\u2019Investigacions M\u00e8diques, 08003 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Riera, M., M\u00e1rquez, E., Clotet, S., Gimeno, J., Roca-Ho, H., Lloreta, J., Juanpere, N., Batlle, D., Pascual, J., and Soler, M.J. 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