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DOI10.1242/jcs.259468
LMBR1L regulates the proliferation and migration of endothelial cells through Norrin/beta-catenin signaling
Liu, Wenjing; Jiang, Xiaoyan; Li, Xiao; Sun, Kuanxiang; Yang, Yeming; Yang, Mu; Li, Shujin; Zhu, Xianjun
通讯作者Yang, M ; Li, SJ ; Zhu, XJ (通讯作者),Univ Elect Sci & Technol China, Sichuan Prov Peoples Hosp, Ctr Med Genet, Sch Med,Sichuan Prov Key Lab Human Dis Gene Study, Chengdu 610072, Sichuan, Peoples R China. ; Zhu, XJ (通讯作者),Chinese Acad Sci, Key Lab Tibetan Med Res, Xining 810008, Qinghai, Peoples R China. ; Zhu, XJ (通讯作者),Northwest Inst Plateau Biol, Qinghai Prov Key Lab Tibetan Med Res, Xining 810008, Qinghai, Peoples R China. ; Yang, M ; Li, SJ ; Zhu, XJ (通讯作者),Sichuan Acad Med Sci, Res Unit Blindness Prevent, 2019RU026, Chengdu 610072, Sichuan, Peoples R China. ; Yang, M ; Li, SJ ; Zhu, XJ (通讯作者),Sichuan Prov Peoples Hosp, Chengdu 610072, Sichuan, Peoples R China. ; Zhu, XJ (通讯作者),First Peoples Hosp Shangqiu, Dept Ophthalmol, Shangqiu 476000, Henan, Peoples R China.
发表日期2022
ISSN0021-9533
EISSN1477-9137
卷号135期号:6
英文摘要Precise Norrin and beta-catenin (Norrin/beta-catenin; encoded by NDP and CTNNB1, respectively) signaling is critical for proper angiogenesis. Dysregulation of this signaling leads to various diseases, of which retinal exudative vitreoretinopathy is the most prevalent. Here, we used a global knockout mouse model to show that limb development membrane protein 1 like (LMBR1L), a transmembrane protein of unknown function in angiogenesis, is essential for retinal vascular development. In vitro experiments revealed that LMBR1L depletion results in aberrant activation of the Norrin/beta-catenin signaling pathway via decreased ubiquitylation of FZD4 and increased Norrin coreceptor LRP5 and p-GSK38-Ser9 expression levels, which cause accumulation of beta-catenin. Moreover, inhibition of LMBR1L in human retinal microvascular endothelial cells (HRECs) caused increased proliferation ability and defective cell migration, which might have occurred as a result of upregulated expression levels of the apical junction components. Treatment with p-GSK3 beta-Ser9 inhibitor AR-A014418 restored the phenotypes in LMBR1L null HRECs, which further demonstrated the important regulatory role of LMBR1L in the Norrin/beta-catenin signaling pathway. Taken together, our data reveal an essential role for LMBR1L in angiogenesis.
关键词FAMILIAL EXUDATIVE VITREORETINOPATHYBETA-CATENINRETINAL ANGIOGENESISVASCULAR DEVELOPMENTWNTFRIZZLED-4MUTATIONSLIPOCALIN-1MECHANISMSEXPRESSION
英文关键词beta-Catenin signaling; Angiogenesis; Knockout model; LMBR1L
语种英语
WOS研究方向Cell Biology
WOS类目Cell Biology
WOS记录号WOS:000779191300015
来源期刊JOURNAL OF CELL SCIENCE
来源机构中国科学院西北生态环境资源研究院
文献类型期刊论文
条目标识符http://gcip.llas.ac.cn/handle/2XKMVOVA/254912
作者单位[Liu, Wenjing; Jiang, Xiaoyan; Li, Xiao; Sun, Kuanxiang; Yang, Yeming; Yang, Mu; Li, Shujin; Zhu, Xianjun] Univ Elect Sci & Technol China, Sichuan Prov Peoples Hosp, Ctr Med Genet, Sch Med,Sichuan Prov Key Lab Human Dis Gene Study, Chengdu 610072, Sichuan, Peoples R China; [Liu, Wenjing; Zhu, Xianjun] Chinese Acad Sci, Key Lab Tibetan Med Res, Xining 810008, Qinghai, Peoples R China; [Liu, Wenjing; Zhu, Xianjun] Northwest Inst Plateau Biol, Qinghai Prov Key Lab Tibetan Med Res, Xining 810008, Qinghai, Peoples R China; [Liu, Wenjing; Yang, Mu; Li, Shujin; Zhu, Xianjun] Sichuan Acad Med Sci, Res Unit Blindness Prevent, 2019RU026, Chengdu 610072, Sichuan, Peoples R China; [Liu, Wenjing; Yang, Mu; Li, Shujin; Zhu, Xianjun] Sichuan Prov Peoples Hosp, Chengdu 610072, Sichuan, Peoples R China; [Zhu, Xianjun] First Peoples Hosp Shangqiu, Dept Ophthalmol, Shangqiu 476000, Henan, Peoples R China
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Liu, Wenjing,Jiang, Xiaoyan,Li, Xiao,et al. LMBR1L regulates the proliferation and migration of endothelial cells through Norrin/beta-catenin signaling[J]. 中国科学院西北生态环境资源研究院,2022,135(6).
APA Liu, Wenjing.,Jiang, Xiaoyan.,Li, Xiao.,Sun, Kuanxiang.,Yang, Yeming.,...&Zhu, Xianjun.(2022).LMBR1L regulates the proliferation and migration of endothelial cells through Norrin/beta-catenin signaling.JOURNAL OF CELL SCIENCE,135(6).
MLA Liu, Wenjing,et al."LMBR1L regulates the proliferation and migration of endothelial cells through Norrin/beta-catenin signaling".JOURNAL OF CELL SCIENCE 135.6(2022).
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