Deletion of p18INK4c aggravates cisplatin‑induced acute kidney injury

Wang,Liang; Chen,Wei; Zhang,Yi; Liu,Chunyan; Yuan,Li; Fu,Lili; Mei,Changlin

doi:10.3892/ijmm.2014.1725

Deletion of p18INK4c aggravates cisplatin‑induced acute kidney injury

Authors:
- Liang Wang
- Wei Chen
- Yi Zhang
- Chunyan Liu
- Li Yuan
- Lili Fu
- Changlin Mei
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Affiliations: Department of Urology, The Second Affiliated Hospital of Dalian Medical University, Dalian 116021, P.R. China, Department of Nephrology, Changzheng Hospital, Shanghai 200003, P.R. China
Published online on: April 4, 2014 https://doi.org/10.3892/ijmm.2014.1725
Pages: 1621-1626

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Abstract

Protection of cyclin-dependent kinase inhibitors (CDKIs) has been demonstrated in acute kidney injury (AKI). However, previous studies on CDKIs have mainly focused on CIP/KIP family members, with INK4 family members rarely being investigated. This study investigated the behaviors of p18INK4c (p18) in cisplatin-induced AKI using p18 gene knockout mice (p18-/-). AKI was induced in p18-/- and wild-type (p18+/+) mice after a single cisplatin (12.5 mg/kg) intraperitoneal injection. Protection by p18 was identified by a comparison of survival, renal function and morphological injuries between p18-/- and p18+/+ mice. Further investigation of endoplasmic reticulum stress (ERS) was performed by western blot analysis in p18-/- and p18+/+ kidneys at day 3 after cisplatin injection. The results revealed that after cisplatin injection, the survival of p18-/- mice was significantly shorter than that of p18+/+ mice, accompanied by aggravated renal function and more severe morphological injuries. Deletion of p18 also significantly aggravated ERS in cisplatin-induced AKI. In conclusion, p18 exerts protective effects on cisplatin‑induced AKI, which may be associated with the effect of p18 on cell death pathways, such as the ERS pathway.

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