Dynamic expression and roles of sequestome‑1/p62 in LPS‑induced acute kidney injury in mice

Li,Ting; Zhao,Jie; Miao,Shuying; Xu,Yunfei; Xiao,Xianzhong; Liu,Ying

doi:10.3892/mmr.2018.8809

Dynamic expression and roles of sequestome‑1/p62 in LPS‑induced acute kidney injury in mice

Authors:
- Ting Li
- Jie Zhao
- Shuying Miao
- Yunfei Xu
- Xianzhong Xiao
- Ying Liu
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Affiliations: Department of Pathophysiology, Xiangya School of Medicine, Central South University, Changsha, Hunan 410078, P.R. China, Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan 410078, P.R. China
Published online on: March 28, 2018 https://doi.org/10.3892/mmr.2018.8809
Pages: 7618-7626
Copyright: © Li 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 one of the most common complications of sepsis. The roles of autophagy in AKI have been demonstrated in previous studies. Sequestosome‑1 (p62) has been demonstrated to serve essential roles in autophagy. The dysregulation of autophagy causes p62 accumulation, which is associated with increased inflammation and tumorigenesis. However, the expression patterns and role of p62 in septic AKI remain unknown. The present study detected the renal autophagy level, and the expression and localization of p62, in a lipopolysaccharide (LPS)‑induced AKI mouse model. The results demonstrated that autophagy was induced in the kidneys of LPS‑treated mice. The mRNA and protein levels of p62 were decreased in whole renal tissue samples and increased in mice treated with LPS. Immunohistochemistry indicated that p62 protein was predominantly expressed in the cytoplasm of proximal tubules under normal conditions and was significantly decreased following LPS injection into the cortex. In addition, p62 protein was gradually redistributed to the outer and inner medullas following treatment with LPS. In vitro experiments demonstrated that overexpression of p62 significantly decreased the viability and increased the lactate dehydrogenase (LDH) release and apoptosis rate, of renal tubular epithelial cells. By contrast, interference with p62 expression using small interfering RNA increased the cell viability and decreased the LDH release and apoptosis rate. The results of the present study demonstrated that p62 may aggravate LPS‑induced acute kidney injury in mice by promoting apoptosis in renal tubular epithelial cells.

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