title: Aldosterone induces NRK-52E cell apoptosis in acute kidney injury via rno-miR-203 hypermethylation and Kim-1 upregulation.
abstract: Acute kidney injury (AKI) is characterized by an acute reduction in kidney function as identified by an increase in serum creatinine levels and reduction in urine output. Kidney injury molecule-1 (Kim-1) is a hallmark of kidney diseases, since it is typically non-detectable in the non-injured kidney, but upregulated and excreted in the urine during AKI. Aldosterone (Aldo) is a mediator of the renin-angiotensin-Aldo system with a pivotal role in the regulation of salt and extracellular fluid metabolism. In the present study, mice subjected to renal ischemia/reperfusion-induced AKI were investigated. The mice exhibited elevated levels of Aldo and angiotensin II, together with increased Kim-1 expression levels in renal tissue. Treatment of the mice with the Aldo receptor antagonist spironolactone decreased Kim-1 expression levels. These results suggest that Aldo may be associated with the expression of Kim-1 during AKI. However, the molecular mechanism underlying the role of Aldo in Kim-1 expression is unclear, and thus was investigated using NRK-52E cells. Aldo was found to induce the apoptosis of NRK-52E cells via the hypermethylation of rno-microRNA (miR)-203 and upregulation of Kim-1. In addition, luciferase reporter assays demonstrated that Kim-1 was a target gene of rno-miR-203 in NRK-52E cells. Furthermore, Aldo-induced NRK-52E cell apoptosis was reduced by treatment with pre-miR-203 and spironolactone to a greater extent when compared with either alone. The results may provide a promising diagnostic marker or novel therapeutic target for AKI.
authors.affiliation: Department of Nephrology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Xiangcheng
authors.initials: X
authors.lastname: Xiao
authors.affiliation: Department of Nephrology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Rong
authors.initials: R
authors.lastname: Tang
authors.affiliation: Department of Nephrology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Zhou
authors.affiliation: The Nephrotic Laboratory of Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Ling
authors.initials: L
authors.lastname: Peng
authors.affiliation: Department of Geriatrics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Pingping
authors.initials: P
authors.lastname: Yu
keywords: acute kidney injury; aldosterone; hypermethylation; kidney injury molecule-1; rno-miR-203