Overexpression of Jagged1 Ameliorates Aged Rat-Derived Endothelial Progenitor Cell Functions and Improves Its Transfusion Efficiency for Rat Balloon-Induced Arterial Injury.
BACKGROUND
Endothelial progenitor cell (EPC) has significant age-dependent alterations in properties, but the role of Jagged1 in aging-induced decline of EPC functions remains unclear.


METHODS
2- and 20-month old healthy male Sprague-Dawley rats were used in present study. Jagged1 gene transfection was performed in EPC isolated from aged (AEPC) and young rats (YEPC), respectively. Experiments were divided into 4 groups: (1) pIRES2-EGFP (PE) group, (2) PE-combined N-[N-(3, 5-difluoro-phenacetyl)-1- alany1]-S-phenyglycine t-butyl ester (DAPT) (PE + D) group, (3) pIRES2 EGFP-Jagged1 (PEJ) group, and (4) PEJ combined DAPT (PEJ + D) group. Notch molecules were detected by real-time quantitative polymerase chain reaction or Western blotting. CD34, CD133, CD45, and KDR markers were detected by flow cytometry. EPC migration and proliferation were detected with a modified Boyden chamber and 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay, respectively; the tube formation ability was assayed by in vitro angiogenesis kit; EPC transfusion after Jagged1 gene transfection was performed in rat carotid artery injury models.


RESULTS
Jagged1 gene transfection effectively activates notch-signaling pathway. Compared with PE groups, overexpression of Jagged1 significantly promoted AEPC functions including proliferation, migration, the tube formation ability, and cell differentiation, these effects could be reasonably diminished by DAPT. In vivo study demonstrated that Jagged1 overexpressing also significantly promoted AEPC homing to the vascular injury sites and decreases the neointima formation after vascular injury.


CONCLUSIONS
Overexpression of Jagged1 ameliorates aged rat-derived EPC functions and increases its transfusion efficiency for balloon-induced rat arterial injury.
Cell Biological Therapy Center, Cell Biological Medicine Integrated Engineering Laboratory of State and Region, Department of Clinical Laboratory, Kunming General Hospital of Chengdu Military Area Command of PLA, Kunming, Yunnan Province, People's Republic of China. Electronic address: zhguxu2001@aliyun.com.
Guangxu
G
Zhu
Cell Biological Therapy Center, Cell Biological Medicine Integrated Engineering Laboratory of State and Region, Department of Clinical Laboratory, Kunming General Hospital of Chengdu Military Area Command of PLA, Kunming, Yunnan Province, People's Republic of China.
Jinxiang
J
Wang
Cardiovascular Institute, Department of Cardiovascular Disease, Xinqiao Hospital, Third Military Medical University, Chongqing, People's Republic of China.
Mingbao
M
Song
Cell Biological Therapy Center, Cell Biological Medicine Integrated Engineering Laboratory of State and Region, Department of Clinical Laboratory, Kunming General Hospital of Chengdu Military Area Command of PLA, Kunming, Yunnan Province, People's Republic of China; Department of Clinical Laboratory, PLA Kunming General Hospital Clinical College of Medicine, Kunming Medical University, Kunming, People's Republic of China.
Fang
F
Zhou
Cell Biological Therapy Center, Cell Biological Medicine Integrated Engineering Laboratory of State and Region, Department of Clinical Laboratory, Kunming General Hospital of Chengdu Military Area Command of PLA, Kunming, Yunnan Province, People's Republic of China.
Dagan
D
Fu
Cell Biological Therapy Center, Cell Biological Medicine Integrated Engineering Laboratory of State and Region, Department of Clinical Laboratory, Kunming General Hospital of Chengdu Military Area Command of PLA, Kunming, Yunnan Province, People's Republic of China.
Guangping
G
Ruan
Cell Biological Therapy Center, Cell Biological Medicine Integrated Engineering Laboratory of State and Region, Department of Clinical Laboratory, Kunming General Hospital of Chengdu Military Area Command of PLA, Kunming, Yunnan Province, People's Republic of China.
Yingying
Y
Bai
Institute of Biological Effect of Electromagnetic Radiation, Department of Occupational Health, School of Military Preventive Medicine, Third Military Medical University, Chongqing, People's Republic of China.
Zhengping
Z
Yu
Cell Biological Therapy Center, Cell Biological Medicine Integrated Engineering Laboratory of State and Region, Department of Clinical Laboratory, Kunming General Hospital of Chengdu Military Area Command of PLA, Kunming, Yunnan Province, People's Republic of China.
Leilei
L
Zhang
Cell Biological Therapy Center, Cell Biological Medicine Integrated Engineering Laboratory of State and Region, Department of Clinical Laboratory, Kunming General Hospital of Chengdu Military Area Command of PLA, Kunming, Yunnan Province, People's Republic of China.
Xiangqing
X
Zhu
Cardiovascular Institute, Department of Cardiovascular Disease, Xinqiao Hospital, Third Military Medical University, Chongqing, People's Republic of China.
Lan
L
Huang
Cell Biological Therapy Center, Cell Biological Medicine Integrated Engineering Laboratory of State and Region, Department of Clinical Laboratory, Kunming General Hospital of Chengdu Military Area Command of PLA, Kunming, Yunnan Province, People's Republic of China.
Rongqing
R
Pang
Cell Biological Therapy Center, Cell Biological Medicine Integrated Engineering Laboratory of State and Region, Department of Clinical Laboratory, Kunming General Hospital of Chengdu Military Area Command of PLA, Kunming, Yunnan Province, People's Republic of China. Electronic address: xinghuapan@aliyun.com.
Xinghua
X
Pan
D000367:Age Factors; D000800:Angioplasty, Balloon / Q000009:adverse effects*; D000818:Animals; D017209:Apoptosis; D020212:Carotid Artery Injuries / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D017536:Carotid Artery, Common / Q000378:metabolism* / Q000473:pathology; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D066026:Endothelial Progenitor Cells / Q000378:metabolism / Q000637:transplantation*; D000072100:Jagged-1 Protein / Q000235:genetics / Q000378:metabolism*; D008297:Male; D058426:Neointima; D018919:Neovascularization, Physiologic; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection; D015854:Up-Regulation
C000606275:Jag1 protein, rat; D000072100:Jagged-1 Protein