期刊论文详细信息
PeerJ
Telomerase reverse transcriptase promotes angiogenesis in neonatal rats after hypoxic-ischemic brain damage
article
Jiao Li1  Yi Feng1  Jing Zhao1  Zhi Fang2  Haiting Liu1 
[1] Department of Pediatrics, West China Second University Hospital, Sichuan University;Department of Cardiovascular Surgery, West China Hospital, Sichuan University
关键词: Angiogenesis;    Blood-brain barrier;    Hypoxic ischemic brain damage;    Neonate;    Telomerase reverse transcriptase;   
DOI  :  10.7717/peerj.14220
学科分类:社会科学、人文和艺术(综合)
来源: Inra
PDF
【 摘 要 】

BackgroundAngiogenesis is an endogenous repair mechanism following hypoxic-ischemic brain damage (HIBD). Interestingly, recent studies have shown that angiogenesis can be regulated by telomerase reverse transcriptase (TERT), a critical component of telomerase. As telomerase reverse transcriptase can promote angiogenesis after stroke, we hypothesized that it could also promote angiogenesis after HIBD. To test this hypothesis, we developed in vivo and in vitro HIBD models in neonatal rats.MethodsTERT was overexpressed by lentivirus and adenovirus infection, and levels were measured using quantitative real-time polymerase chain reaction. We used a cell counting kit to quantify the proliferation rate of brain microvascular endothelial cells (BMECs), and immunofluorescence staining to measure CD34 expression levels. A microvessel formation assay was used to evaluate angiogenesis. Blood-brain barrier (BBB) integrity was assessed using immunohistochemical staining for ZO-1 and Evans Blue staining. Lastly, the expression level of Notch-1 was measured by western blotting.ResultsOverexpression of TERT promoted the proliferation of BMECs after hypoxic-ischemic damage in vitro. TERT overexpression increased the formation of microvessels in the neonatal brain after HIBD both in vivo and in vitro. Overexpression of TERT improved BBB integrity in the brains of neonatal rats after HIBD. In addition, the expression level of Notch-1 was increased in BMECs following oxygen glucose deprivation, and overexpression of TERT further increased Notch-1 expression levels in BMECs following oxygen glucose deprivation.DiscussionOur results reveal that telomerase reverse transcriptase promotes angiogenesis and maintains the integrity of the blood-brain barrier after neonatal hypoxic-ischemic brain damage. Furthermore, the Notch-1 signaling pathway appears to contribute to the angiogenic function of telomerase reverse transcriptase. This protective effect of telomerase reverse transcriptase opens new horizons for future investigations aimed at uncovering the full potential of telomerase reverse transcriptase as a promising new target for the treatment of hypoxic-ischemic encephalopathy.

【 授权许可】

CC BY   

【 预 览 】
附件列表
Files Size Format View
RO202307100003227ZK.pdf 4806KB PDF download
  文献评价指标  
  下载次数:0次 浏览次数:0次