Dynamic changes of cell cycle elements in the ischemic brain after bone marrow stromal cells transplantation in rats.
Transplantation of bone marrow stromal cells (BMSCs) improves animal neurological functional recovery after stroke. But the mechanism remains unclear. As cell cycle machinery plays an important role in stroke, we investigated the dynamic changes of cell cycle elements in a rat model of middle cerebral artery occlusion. We found the cell cycle markers, cdk4 along with its activator cyclin D1, and proliferating cell nuclear antigen (PCNA), increased after brain ischemia-reperfusion. Phosphorylation of the retinoblastoma protein (pRb, on ser-795), the cyclin D/cdk4 complex mutual target, was upregulated accordingly. However, intravenously administrated BMSCs facilitated cyclin D1, cdk4, and PCNA decrease in the ischemic cortex. Meanwhile, phospho-pRb (ser-795) was completely inhibited. On the contrary, endogenous cdk inhibitor p27 reduced before but enhanced after BMSCs treatment. These findings suggested BMSCs might modulate cell cycle progression in injured brain via downregulation of the cyclin D1/cdk4/pRb pathway as well as upregulation of p27 level. These results provide another way by which BMSCs may contribute to the recovery from stroke.
Cai
Kefu
K
Department of Neurology, Nanjing Brain Hospital, Nanjing Medical University, No. 264 Guangzhou Road, Nanjing 210029, China.
Di
Qing
Q
Shi
Jingping
J
Zhang
Yingdong
Y
D000818:Animals; D016026:Bone Marrow Transplantation; D002545:Brain Ischemia / Q000503:physiopathology* / Q000601:surgery*; D002453:Cell Cycle / Q000502:physiology*; D002540:Cerebral Cortex / Q000503:physiopathology / Q000601:surgery; D019938:Cyclin D1 / Q000378:metabolism; D051358:Cyclin-Dependent Kinase 4 / Q000378:metabolism; D004195:Disease Models, Animal; D020244:Infarction, Middle Cerebral Artery / Q000503:physiopathology / Q000601:surgery; D008297:Male; D010766:Phosphorylation; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016160:Retinoblastoma Protein / Q000378:metabolism; D015398:Signal Transduction; D020521:Stroke / Q000503:physiopathology / Q000601:surgery; D017154:Stromal Cells / Q000637:transplantation*
C530106:Ccnd1 protein, rat; D018809:Proliferating Cell Nuclear Antigen; D016160:Retinoblastoma Protein; D019938:Cyclin D1; C495903:Cdk4 protein, rat; D051358:Cyclin-Dependent Kinase 4