环状RNAcircZNF609调控miR-184/HPSE信号轴在角膜淋巴管增生中的作用机制研究
批准号:
82000855
项目类别:
青年科学基金项目
资助金额:
24.0 万元
负责人:
林通
依托单位:
学科分类:
角膜及眼表疾病
结题年份:
2023
批准年份:
2020
项目状态:
已结题
项目参与者:
林通
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中文摘要
角膜淋巴管增生是角膜移植排斥的高危因素。环状RNA在免疫炎症疾病中发挥重要调控作用。我们前期通过高通量芯片检测发现淋巴管内皮细胞炎症诱导下环状RNAcZNF609表达显著上调,并证实在淋巴管增生病理状态下人和小鼠角膜中cZNF609表达上调。生物信息学分析发现cZNF609与角膜中含量最丰富的微小RNAmiR-184存在互补结合序列,而miR-184已证实参与调控角膜淋巴管增生。我们推测cZNF609可能通过结合miR-184,解除其对靶基因抑制作用,进而调控角膜淋巴管增生。我们发现与miR-184存在结合序列的乙酰肝素酶(HPSE)在炎症诱导角膜淋巴管增生组织中表达增强,因此本课题拟通过表达分布规律、生物学功能、分子机制和应用探究四个层面验证cZNF609通过miR-184/HPSE信号轴调控角膜淋巴管增生,有助于揭示环状RNA在淋巴管增生中的作用机制,为角膜移植排斥提供新的干预靶点。
英文摘要
Corneal lymphangiogenesis has been considered as a high risk factor of corneal graft rejection. CircrRNA plays an important regulatory role in immune inflammatory diseases. Our previous study showed up-regulated expression of cZNF609 in the inflammatory lymphatic endothelial cells by microarray analysis, and we then confirmed that the lymphangitic corneas from both human and mice showed up-regulated expression of cZNF609.By the biological information analysis, cZNF609 has complementary base sequences with miR184 which is the most abundant micro RNA in the cornea, and miR184 has been confirmed to participate in corneal lymphangiogenesis.Based on these evidences, we speculate that cZNF609 could sponge miR184 and then remove its inhibitory effect on target genes, and thus regulate cornea lymphangiogenesis. We found that the expression of heparinase (HPSE) which has a binding sequence to mir-184 was enhanced in inflammatory corneal lymphangiogenesis. Thus this study intends to investigate the role of circZNF609 in corneal lymphangiogenesis by regulation of microRNA-184 /HPSE signal axis, through four aspects of studies including express distribution, biological function, molecular mechanisms and application, and this study contributes to reveal the mechanism of circrRNA in lymphangiogenesis, and finally provide new targets for the intervention of corneal graft rejection.
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DOI:10.1007/s00417-023-06141-x
发表时间:2023-06-21
期刊:GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
影响因子:2.7
作者:Zhou,Yemeng;Wang,Wushuang;Gong,Lan
通讯作者:Gong,Lan
DOI:10.3389/fmed.2021.769448
发表时间:2021
期刊:Frontiers in medicine
影响因子:3.9
作者:Lin T;Wang W;Lu Y;Gong L
通讯作者:Gong L
DOI:10.7150/ijms.76603
发表时间:2023
期刊:International journal of medical sciences
影响因子:3.6
作者:Liu W;Lin T;Gong L
通讯作者:Gong L
DOI:10.1007/s11356-023-25605-5
发表时间:2023-02
期刊:Environmental Science and Pollution Research
影响因子:5.8
作者:Han Zhao;Tong Lin;Yun Yang;Changming Feng;Wushuang Wang;Lan Gong
通讯作者:Han Zhao;Tong Lin;Yun Yang;Changming Feng;Wushuang Wang;Lan Gong
DOI:--
发表时间:2023
期刊:J Glob Health
影响因子:--
作者:Han Zhao;Yun Yang;Changming Feng;Wushuang Wang;Chenhao Yang;Yue Yin;Lan Gong;Tong Lin
通讯作者:Tong Lin
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