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学科主题: 临床医学
题名:
The Effects of Pleiotrophin in Proliferative Diabetic Retinopathy
作者: Zhu, Xuemei; Bai, Yujing; Yu, Wenzhen; Pan, Chungting; Jin, Enzhong; Song, Dan; Xu, Qiong; Yao, Yuou; Huang, Lvzhen; Tao, Yong; Li, Xiaoxin; Zhao, Mingwei
刊名: PLOS ONE
发表日期: 2015-01-24
DOI: 10.1371/journal.pone.0115523
卷: 10, 期:1
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Multidisciplinary Sciences
研究领域[WOS]: Science & Technology - Other Topics
关键词[WOS]: ANAPLASTIC LYMPHOMA KINASE ; GLYCATION END-PRODUCTS ; SIGNALING PATHWAYS ; PANCREATIC-CANCER ; ENDOTHELIAL-CELLS ; NEURAL APOPTOSIS ; VEGF EXPRESSION ; SEMAPHORIN 3A ; GROWTH ; RAT
英文摘要:

Pleiotrophin (PTN), a secreted, multifunctional cytokine, is involved in angiogenic, fibrotic and neurodegenerative diseases. However, little is known about its effects on diabetic retinopathy, a neurovascular disease. To investigate the role of PTN in proliferative diabetic retinopathy (PDR), PTN concentration in the vitreous was evaluated in PDR patients and non-diabetic controls. PTN expression was observed in epiretinal membranes from patients. PTN knockdown was performed using small interfering (si) RNA, and the effects on retinal pigment epithelium (RPE) cells and human umbilical vascular endothelia cells (HUVECs) were observed in vitro under hyperglycemic and hypoxic conditions. Cell attachment, proliferation, migration, tube formation, cell cycle, apoptosis, extracellular signal-regulated kinase 1/2 (ERK 1/2) phosphorylation, and VEGF levels were studied. The vitreous PTN concentration in PDR patients was higher than that in non-diabetic controls, and PTN was highly expressed in the fibrovascular membranes of PDR patients. Under hyperglycemic and hypoxic conditions, PTN knockdown reduced cell attachment, proliferation, migration, and tube formation and induced cell cycle arrest and apoptosis in vitro. Mechanically, PTN depletion decreased ERK 1/2 phosphorylation. Recombinant PTN up regulated the concentration of VEGF in vitro, which can be attenuated by the ERK 1/2 inhibitor. Taken together, our results implied that elevated PTN in PDR patients might participate in the critical processes of the development of PDR, most likely playing roles in angiogenesis and proliferation, possibly by activating the ERK 1/2 pathway and regulating VEGF secretion. These findings provide new insight into the roles of PTN in PDR and suggest that PTN may become a new target for therapeutic intervention in PDR.

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语种: 英语
所属项目编号: 20130001110086
项目资助者: Specialized Research Fund for the Doctoral Program of Higher Education
WOS记录号: WOS:000350336000005
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/54138
Appears in Collections:北京大学第二临床医学院_期刊论文

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作者单位: Peking Univ, Peoples Hosp, Dept Ophthalmol,Minist Educ, Key Lab Vis Loss & Restorat,Beijing Key Lab Diago, Beijing 100044, Peoples R China

Recommended Citation:
Zhu, Xuemei,Bai, Yujing,Yu, Wenzhen,et al. The Effects of Pleiotrophin in Proliferative Diabetic Retinopathy[J]. PLOS ONE,2015,10(1).
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