Deletion of p18(INK4c) aggravates cisplatin-induced acute kidney injury.
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 p18(INK4c) (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.
Department of Urology, The Second Affiliated Hospital of Dalian Medical University, Dalian 116021, P.R. China.
Liang
L
Wang
Department of Nephrology, Changzheng Hospital, Shanghai 200003, P.R. China.
Wei
W
Chen
Department of Nephrology, Changzheng Hospital, Shanghai 200003, P.R. China.
Yi
Y
Zhang
Department of Urology, The Second Affiliated Hospital of Dalian Medical University, Dalian 116021, P.R. China.
Chunyan
C
Liu
Department of Nephrology, Changzheng Hospital, Shanghai 200003, P.R. China.
Li
L
Yuan
Department of Nephrology, Changzheng Hospital, Shanghai 200003, P.R. China.
Lili
L
Fu
Department of Nephrology, Changzheng Hospital, Shanghai 200003, P.R. China.
Changlin
C
Mei
D058186:Acute Kidney Injury / Q000139:chemically induced* / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D015153:Blotting, Western; D002945:Cisplatin / Q000633:toxicity*; D050763:Cyclin-Dependent Kinase Inhibitor p18 / Q000172:deficiency* / Q000235:genetics; D020287:In Situ Nick-End Labeling; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D016133:Polymerase Chain Reaction
D050763:Cyclin-Dependent Kinase Inhibitor p18; D002945:Cisplatin