{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T06:23:49Z","timestamp":1787207029284,"version":"build-2736575974"},"reference-count":82,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T00:00:00Z","timestamp":1787184000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      Subclinical Diabetic Kidney Disease (\n                      <jats:sub>sub<\/jats:sub>\n                      DKD) is a clinically silent stage of kidney disease secondary to diabetes\n                      <jats:italic>mellitus<\/jats:italic>\n                      (DM), being a public health problem worldwide. The pathogenic mechanism involves hyperglycemia-induced tubulointerstitial injury associated with dysfunction of tubular protein reabsorption and proteinuria, even without any clinical signs like impaired glomerular function. Interestingly, angiotensin receptor blockers (ARBs), known as type 1 angiotensin II receptor (AT\n                      <jats:sub>1<\/jats:sub>\n                      R) antagonists, are effective against proteinuria in many kidney diseases, suggesting the potential involvement of the Renin-Angiotensin System. Herein, we studied the potential renoprotective effects of ARB on the pathogenesis of\n                      <jats:sub>sub<\/jats:sub>\n                      DKD.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      For that, we developed streptozotocin (STZ)-induced type 1 DM [with normal levels of glomerular flow rate] in male Wistar rats, which were daily treated with 30 mg\/kg\/day losartan, a well-known ARB, via gavage for 6 consecutive weeks starting after induction of diabetes. Four experimental groups were generated: 1) CONT, normoglycemic rat; 2) ARB, normoglycemic rat treated with losartan; 3)\n                      <jats:sub>sub<\/jats:sub>\n                      DKD, diabetic rat; 4)\n                      <jats:sub>sub<\/jats:sub>\n                      DKD+ARB, diabetic rat treated with losartan.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Comparing with the CONT group, the\n                      <jats:sub>sub<\/jats:sub>\n                      DKD group presented: 1) impaired tubular reabsorption of Na+ and Cl-; 2) proteinuria associated with dysfunction in cortical albumin endocytosis; 3) increased levels of urinary lactate dehydrogenase and \u03b3-glutamyltransferase, markers of kidney and proximal tubule epithelial cell injuries, respectively; 4) increased kidney injury score and tubulointerstitial injury; 5) increased cortical type 1 collagen deposition. Interestingly, the ARB treatment ameliorated all parameters observed in diabetic rats (\n                      <jats:sub>sub<\/jats:sub>\n                      DKD+ARB group). No significant changes were observed in the ARB group.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Altogether, our findings indicated that ARB promotes renoprotective effects by attenuating AT1R-associated tubular damage and proteinuria of tubular origin observed in subDKD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1871708","type":"journal-article","created":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T05:28:12Z","timestamp":1787203692000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Angiotensin receptor blocker ameliorates the development of tubulointerstitial injury and fibrosis associated with tubular proteinuria observed in subclinical diabetic kidney disease"],"prefix":"10.3389","volume":"17","author":[{"given":"Mariana R.","family":"Campos","sequence":"first","affiliation":[{"name":"Department of Physiology and Biophysics, Institute of Biological Sciences, Federal University of Minas Gerais","place":["Belo Horizonte, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro Henrique S. R.","family":"Seabra","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics, Institute of Biological Sciences, Federal University of Minas Gerais","place":["Belo Horizonte, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura B. F.","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics, Institute of Biological Sciences, Federal University of Minas Gerais","place":["Belo Horizonte, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vit\u00f3ria L.","family":"Lacerda","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics, Institute of Biological Sciences, Federal University of Minas Gerais","place":["Belo Horizonte, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tawanne M.","family":"Souza","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics, Institute of Biological Sciences, Federal University of Minas Gerais","place":["Belo Horizonte, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariana C.","family":"Moraes","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics, Institute of Biological Sciences, Federal University of Minas Gerais","place":["Belo Horizonte, Brazil"]},{"name":"Department of Pharmacology, Institute of Biological Sciences, Federal University of Minas Gerais","place":["Belo Horizonte, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Let\u00edcia Cristine C.","family":"dos Santos","sequence":"additional","affiliation":[{"name":"Department of General Pathology, Institute of Biological Sciences, Federal University of Minas Gerais","place":["Belo Horizonte, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula P.","family":"Campos","sequence":"additional","affiliation":[{"name":"Department of General Pathology, Institute of Biological Sciences, Federal University of Minas Gerais","place":["Belo Horizonte, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celso","family":"Caruso-Neves","sequence":"additional","affiliation":[{"name":"Carlos Chagas Filho Biophysics Institute, Federal University of Rio de Janeiro","place":["Rio de Janeiro, Brazil"]},{"name":"National Institute of Advanced Technologies in Diagnosis and Prognosis of Chronic and Neglected Diseases, INATEC","place":["Rio de Janeiro, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diogo B.","family":"Peruchetti","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics, Institute of Biological Sciences, Federal University of Minas Gerais","place":["Belo Horizonte, Brazil"]},{"name":"National Institute of Science and Technology in Nanobiopharmaceutics, INCT-Nanobiofar","place":["Belo Horizonte, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,20]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"130684","DOI":"10.1016\/j.bbagen.2024.130684","article-title":"The angiotensin II\/type 1 angiotensin II receptor pathway is implicated in the dysfunction of albumin endocytosis in renal proximal tubule epithelial cells induced by high glucose levels","volume":"1868","author":"Afonso","year":"2024","journal-title":"Biochim. 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