Acute renal failure during sepsis: potential role of cell cycle regulation.
OBJECTIVE
This study aimed to evaluate cell cycle regulation in acute kidney injury after intraperitoneal sepsis in rats.


METHODS
Polymicrobial sepsis was induced by cecal ligation and puncture (CLP) in rats. At 0, 6, 12, 24, 48, and 72 h after CLP, serum creatinine was evaluated. DNA content of isolated kidney cells was analyzed using flow cytometer. Furthermore, the expression of p21, p53, cyclin D1, cyclin E, CDK2, CDK4 and P-pRb was also measured by western blot.


RESULTS
After sepsis-induced by CLP, kidney injury of rat was associated with G1 cell cycle arrest, however, recovery of renal function related to cell cycle progression 48h after CLP. Results also showed that the upregulation of p53 and p21 was correlated with G1 cell arrest in 48h after CLP. Nevertheless, upregulation of cyclin D1/CDK4 and cyclin E/CDK2 induced pRb phosphorylation, which resulted in the G1/S transition 48 h after CLP.


CONCLUSIONS
The data suggest that G1 cell cycle arrest may play a role in the initiation of kidney injury, whereas, through regulating cell cycle, p53, p21, CDKs, cyclins and P-pRb may be involved in the injury or recovery of renal function after intraperitoneal sepsis.
Yang
Quan-Hui
QH
Department of Critical Care Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, 1 Shuaifuyuan, Dongcheng District, Beijing, 100730, China.
Liu
Da-Wei
DW
Long
Yun
Y
Liu
Hong-Zhong
HZ
Chai
Wen-Zhao
WZ
Wang
Xiao-Ting
XT
D058186:Acute Kidney Injury / Q000473:pathology / Q000503:physiopathology*; D000818:Animals; D002453:Cell Cycle / Q000235:genetics* / Q000502:physiology; D003404:Creatinine / Q000097:blood; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D019927:Cyclin E / Q000235:genetics / Q000378:metabolism; D051357:Cyclin-Dependent Kinase 2 / Q000235:genetics / Q000378:metabolism; D051358:Cyclin-Dependent Kinase 4 / Q000235:genetics / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism; D016213:Cyclins / Q000235:genetics / Q000378:metabolism; D004247:DNA / Q000032:analysis; D004195:Disease Models, Animal; D005434:Flow Cytometry; D016193:G1 Phase / Q000235:genetics / Q000502:physiology; D008297:Male; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D016160:Retinoblastoma Protein / Q000235:genetics / Q000378:metabolism; D016196:S Phase / Q000235:genetics / Q000502:physiology; D018805:Sepsis / Q000503:physiopathology*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
D019927:Cyclin E; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53; D019938:Cyclin D1; D004247:DNA; D003404:Creatinine; D051357:Cyclin-Dependent Kinase 2; D051358:Cyclin-Dependent Kinase 4