{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T09:23:17Z","timestamp":1771233797910,"version":"3.50.1"},"reference-count":48,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2022,6,21]],"date-time":"2022-06-21T00:00:00Z","timestamp":1655769600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institutes of Health","award":["5-R01-DK104708"],"award-info":[{"award-number":["5-R01-DK104708"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Canonical transient receptor potential-6 (TRPC6) channels have been implicated in familial and acquired forms of focal and segmental glomerulosclerosis (FSGS), and in renal fibrosis following ureteral obstruction in mice. TRPC6 channels also appear to play a role in driving glomerular disease in aging and in autoimmune glomerulonephritis. In the present study, we examine the role of TRPC6 in the proteinuric state caused by prolonged albumin overload (AO) in Sprague Dawley rats induced by daily injections of exogenous albumin. This was assessed in rats with a global and constitutive inactivation of TRPC6 channels (Trpc6del\/del rats) and in wild-type littermates (Trpc6wt\/wt rats). AO for 14 and 28 days caused increased urine albumin excretion that was significantly attenuated in Trpc6del\/del rats compared to Trpc6wt\/wt controls. AO overload did not induce significant glomerulosclerosis or azotemia in either genotype. AO induced mild tubulointerstitial disease characterized by fibrosis, hypercellularity and increased expression of markers of fibrosis and inflammation. Those changes were equally severe in Trpc6wt\/wt and Trpc6del\/del rats. Immunoblot analysis of renal cortex indicated that AO increased the abundances of TRPC3 and TRPC6, and caused a nearly complete loss of TRPC5 in Trpc6wt\/wt rats. The increase in TRPC3 and the loss of TRPC5 occurred to the same extent in Trpc6del\/del rats. These data also suggest that TRPC6 plays a role in the normal function of the glomerular filtration barrier. However, whether TRPC6 inactivation protects the tubulointerstitial compartments in Sprague Dawley rats depends on the disease model examined.<\/jats:p>","DOI":"10.3390\/cells11131985","type":"journal-article","created":{"date-parts":[[2022,6,21]],"date-time":"2022-06-21T21:55:19Z","timestamp":1655848519000},"page":"1985","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["TRPC6 Inactivation Reduces Albuminuria Induced by Protein Overload in Sprague Dawley Rats"],"prefix":"10.3390","volume":"11","author":[{"given":"Eun Young","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Biology and Biochemistry, University of Houston, Houston, TX 77204, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stuart E.","family":"Dryer","sequence":"additional","affiliation":[{"name":"Department of Biology and Biochemistry, University of Houston, Houston, TX 77204, USA"},{"name":"Department of Biomedical Sciences, Tilman J. Fertitta Family College of Medicine, University of Houston, Houston, TX 77204, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.1016\/j.bbadis.2019.04.001","article-title":"TRPC channels: Regulation, dysregulation and contributions to chronic kidney disease","volume":"1865","author":"Dryer","year":"2019","journal-title":"Biochim. Biophys. Acta (BBA)-Mol. 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