{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T10:07:07Z","timestamp":1792318027396,"version":"4.4.0"},"reference-count":67,"publisher":"Portland Press Ltd.","issue":"7","license":[{"start":{"date-parts":[[2021,4,6]],"date-time":"2021-04-06T00:00:00Z","timestamp":1617667200000},"content-version":"vor","delay-in-days":5,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0\/"}],"content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,4,16]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Clinical trials indicate that sodium\/glucose co-transporter 2 (SGLT2) inhibitors (SGLT2i) improve kidney function, yet, the molecular regulation of SGLT2 expression is incompletely understood. Here, we investigated the role of the intrarenal renin\u2013angiotensin system (RAS) on SGLT2 expression. In adult non-diabetic participants in the Nephrotic Syndrome Study Network (NEPTUNE, n=163), multivariable linear regression analysis showed SGLT2 mRNA was significantly associated with angiotensinogen (AGT), renin, and angiotensin-converting enzyme (ACE) mRNA levels (P&amp;lt;0.001). In vitro, angiotensin II (Ang II) dose-dependently stimulated SGLT2 expression in HK-2, human immortalized renal proximal tubular cells (RPTCs); losartan and antioxidants inhibited it. Sglt2 expression was increased in transgenic (Tg) mice specifically overexpressing Agt in their RPTCs, as well as in WT mice with a single subcutaneous injection of Ang II (1.44 mg\/kg). Moreover, Ang II (1000 ng\/kg\/min) infusion via osmotic mini-pump in WT mice for 4 weeks increased systolic blood pressure (SBP), glomerulosclerosis, tubulointerstitial fibrosis, and albuminuria; canaglifozin (Cana, 15 mg\/kg\/day) reversed these changes, with the exception of SBP. Fractional glucose excretion (FeGlu) was higher in Ang II+Cana than WT+Cana, whereas Sglt2 expression was similar. Our data demonstrate a link between intrarenal RAS and SGLT2 expression and that SGLT2i ameliorates Ang II-induced renal injury independent of SBP.<\/jats:p>","DOI":"10.1042\/cs20210094","type":"journal-article","created":{"date-parts":[[2021,4,6]],"date-time":"2021-04-06T14:37:45Z","timestamp":1617719865000},"page":"943-961","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":67,"title":["Angiotensin II up-regulates sodium-glucose co-transporter 2 expression and SGLT2 inhibitor attenuates Ang II-induced hypertensive renal injury in mice"],"prefix":"10.1042","volume":"135","author":[{"given":"Kana\u00a0N.","family":"Miyata","sequence":"first","affiliation":[{"name":"D\u00e9partement de M\u00e9decine, Universit\u00e9 de Montr\u00e9al, Centre de recherche du Centre hospitalier de l\u2019Universit\u00e9 de Montr\u00e9al (CRCHUM), Tour Viger-Pavillon R, 900 Saint Denis Street, Montr\u00e9al, Quebec H2X 0A9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0645-7987","authenticated-orcid":false,"given":"Chao-Sheng","family":"Lo","sequence":"additional","affiliation":[{"name":"D\u00e9partement de M\u00e9decine, Universit\u00e9 de Montr\u00e9al, Centre de recherche du Centre hospitalier de l\u2019Universit\u00e9 de Montr\u00e9al (CRCHUM), Tour Viger-Pavillon R, 900 Saint Denis Street, Montr\u00e9al, Quebec H2X 0A9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuiling","family":"Zhao","sequence":"additional","affiliation":[{"name":"D\u00e9partement de M\u00e9decine, Universit\u00e9 de Montr\u00e9al, Centre de recherche du Centre hospitalier de l\u2019Universit\u00e9 de Montr\u00e9al (CRCHUM), Tour Viger-Pavillon R, 900 Saint Denis Street, Montr\u00e9al, Quebec H2X 0A9, 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de recherche du Centre hospitalier de l\u2019Universit\u00e9 de Montr\u00e9al (CRCHUM), Tour Viger-Pavillon R, 900 Saint Denis Street, Montr\u00e9al, Quebec H2X 0A9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junzheng","family":"Peng","sequence":"additional","affiliation":[{"name":"D\u00e9partement de M\u00e9decine, Universit\u00e9 de Montr\u00e9al, Centre de recherche du Centre hospitalier de l\u2019Universit\u00e9 de Montr\u00e9al (CRCHUM), Tour Viger-Pavillon R, 900 Saint Denis Street, Montr\u00e9al, Quebec H2X 0A9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Kretzler","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, University of Michigan, 1560 MSRB II, 1150 West Medical Center Drive, SPC5676, Ann Arbor, MI 48109, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janos\u00a0G.","family":"Filep","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Montr\u00e9al, Centre de recherche de l\u2019Hopital Maisonneuve-Rosemont, 5415 boul. l\u2019Assomption, Montr\u00e9al, Quebec H1T 2M4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie\u00a0R.","family":"Ingelfinger","sequence":"additional","affiliation":[{"name":"Pediatric Nephrology Unit, Harvard Medical School, Massachusetts General Hospital, 15 Parkman Street, WAC 709, Boston, MA 02114, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5255-6970","authenticated-orcid":false,"given":"Shao-Ling","family":"Zhang","sequence":"additional","affiliation":[{"name":"D\u00e9partement de M\u00e9decine, Universit\u00e9 de Montr\u00e9al, Centre de recherche du Centre hospitalier de l\u2019Universit\u00e9 de Montr\u00e9al (CRCHUM), Tour Viger-Pavillon R, 900 Saint Denis Street, Montr\u00e9al, Quebec H2X 0A9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7137-454X","authenticated-orcid":false,"given":"John\u00a0S.D.","family":"Chan","sequence":"additional","affiliation":[{"name":"D\u00e9partement de M\u00e9decine, Universit\u00e9 de Montr\u00e9al, Centre de recherche du Centre hospitalier de l\u2019Universit\u00e9 de Montr\u00e9al (CRCHUM), Tour Viger-Pavillon R, 900 Saint Denis Street, Montr\u00e9al, Quebec H2X 0A9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2021,4,14]]},"reference":[{"key":"2021113011204093200_B1","doi-asserted-by":"publisher","first-page":"2295","DOI":"10.1056\/NEJMoa1811744","article-title":"Canagliflozin and renal outcomes in type 2 diabetes and nephropathy","volume":"380","author":"Perkovic","year":"2019","journal-title":"N. 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