Aldosterone induces NRK‑52E cell apoptosis in acute kidney injury via rno‑miR‑203 hypermethylation and Kim-1 upregulation

Xiao,Xiangcheng; Tang,Rong; Zhou,Xiao; Peng,Ling; Yu,Pingping

doi:10.3892/etm.2016.3443

Aldosterone induces NRK‑52E cell apoptosis in acute kidney injury via rno‑miR‑203 hypermethylation and Kim-1 upregulation

Authors:
- Xiangcheng Xiao
- Rong Tang
- Xiao Zhou
- Ling Peng
- Pingping Yu
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Affiliations: Department of Nephrology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China, The Nephrotic Laboratory of Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China, Department of Geriatrics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China
Published online on: June 8, 2016 https://doi.org/10.3892/etm.2016.3443
Pages: 915-924
Copyright: © Xiao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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.

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