biostudies-literatureLazelle RANIDDK NIH HHSNIGMS NIH HHS1456-64https://www.ebi.ac.uk/biostudies/studies/S-EPMC4849833biostudies-literatureUnknown27(5)Tacrolimus is a widely used immunosuppressive drug that inhibits the phosphatase calcineurin when bound to the 12 kDa FK506-binding protein (FKBP12). When this binding occurs in T cells, it leads to immunosuppression. Tacrolimus also causes side effects, however, such as hypertension and hyperkalemia. Previously, we reported that tacrolimus stimulates the renal thiazide-sensitive sodium chloride cotransporter (NCC), which is necessary for the development of hypertension. However, it was unclear if tacrolimus-induced hypertension resulted from tacrolimus effects in renal epithelial cells directly or in extrarenal tissues, and whether inhibition of calcineurin was required. To address these questions, we developed a mouse model in which FKBP12 could be deleted along the nephron. FKBP12 disruJournal of the American Society of Nephrology : JASNRenal Deletion of 12 kDa FK506-Binding Protein Attenuates Tacrolimus-Induced Hypertension.PMC4849833R01 DK095841T32 DK067864T32 GM071338R01 DK051496Terker ASBlankenstein KIHimmerkus NEllison DHLazelle RAYang CLBleich MMcCully BHMutig KBachmann SfalseRenal Deletion of 12 kDa FK506-Binding Protein Attenuates Tacrolimus-Induced Hypertension.Tacrolimus is a widely used immunosuppressive drug that inhibits the phosphatase calcineurin when bound to the 12 kDa FK506-binding protein (FKBP12). When this binding occurs in T cells, it leads to immunosuppression. Tacrolimus also causes side effects, however, such as hypertension and hyperkalemia. Previously, we reported that tacrolimus stimulates the renal thiazide-sensitive sodium chloride cotransporter (NCC), which is necessary for the development of hypertension. However, it was unclear if tacrolimus-induced hypertension resulted from tacrolimus effects in renal epithelial cells directly or in extrarenal tissues, and whether inhibition of calcineurin was required. To address these questions, we developed a mouse model in which FKBP12 could be deleted along the nephron. FKBP12 disru2016-01-01T00:00:00Z2016 May2025-04-04T07:30:39.012Z2019-03-27T02:12:40ZS-EPMC48498332643290410.1681/ASN.201504046610.1681/asn.2015040466