E3泛素连接酶RNF5在急性肺损伤中的作用及分子机制研究

批准号:
81970070
项目类别:
面上项目
资助金额:
55.0 万元
负责人:
张晓晶
依托单位:
学科分类:
急性肺损伤和急性呼吸窘迫综合征
结题年份:
2023
批准年份:
2019
项目状态:
已结题
项目参与者:
张晓晶
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中文摘要
急性肺损伤是致死性呼吸系统危重症,发病机制尚未完全明确,目前除机械通气和限制液体进入量等辅助手段外,无临床有效治疗策略。泛素化系统广泛参与肺动态平衡和疾病过程。E3泛素连接酶RING指蛋白5(RNF5)是泛素化系统关键调控子,然而RNF5在肺脏疾病中的作用和机制国内外未见报道。本项目前期研究发现,RNF5表达水平随急性肺损伤的进程显著下调。Rnf5敲除小鼠表现出明显加重的由脂多糖诱导的小鼠肺泡结构破坏、肺水肿和炎症反应,提示RNF5在急性肺损伤中发挥关键调控作用。本项目拟通过Rnf5敲除和过表达基因工程小鼠急性肺损伤模型,采用多组学高通量筛选技术结合多种分子生物学手段,从动物、细胞和分子水平系统阐明RNF5调控急性肺损伤的功能和机制。本项目以期为深入理解急性肺损伤提供新思路,为急性肺损伤及相关呼吸系统危重症的药物开发提供新靶点和新策略。
英文摘要
Acute lung injury (ALI) is a lethal respiratory disease with the pathogenesis not fully understood. There is no approved pharmacological intervention for ALI therapy, expect for certain adjuvant approaches like mechanical ventilation or limiting liquid inflow. The ubiquitination-proteasome system (UPS) extensively participates in the lung homeostasis and pathophysiologic process. RING finger protein 5 (RNF5) is an E3 ubiquitin ligase serving as key regulator in the UPS-based protein degradation or activation. However, the role of RNF5 in ALI is unknown. In our preliminary study, we observed a dramatic downregulation of RNF5 during ALI progression. Furthermore, Rnf5-knockout mice showed significantly exacerbated alveolar damage, pulmonary edema and inflammatory response compared to wild type controls in lipopolysaccharide-induced ALI model. These preliminary findings suggest a close participation of RNF5 in ALI development. In this project, we aimed to demonstrate the regulatory function of RNF5 on ALI progress and to clarify the in-depth mechanisms, which will be achieved by substantial experiments at the animal, cell and molecular levels applying multi-omics screening technology in combination with molecular biological methods. The achievements of this project will further our understanding on ALI and pave the way for developing promising interventional targets and therapeutic strategies to treat ALI and related respiratory diseases.
期刊论文列表
专著列表
科研奖励列表
会议论文列表
专利列表
DOI:10.1126/scitranslmed.abg8117
发表时间:2021-12
期刊:Science Translational Medicine
影响因子:17.1
作者:Xiao-Jing Zhang;Zhi‐Gang She;Junyong Wang;Dating Sun;L. Shen;H. Xiang;Xu Cheng;Yan‐Xiao Ji;Yong-Ping Huang;Peng-Long Li;Xia Yang;Yanjie Cheng;Jun-Peng Ma;Haiping Wang;Yufeng Hu;Fengjiao Hu;S. Tian;Han Tian;Peng Zhang;Guang-Nian Zhao;Lin Wang;Manli Hu;Qin Yang;Lihua Zhu;Jingjing Cai;Juan Yang;Xin Zhang;Xinliang Ma;Qingbo Xu;R. Touyz;Peter P. Liu;R. Loomba;Yibin Wang;Hongliang Li
通讯作者:Xiao-Jing Zhang;Zhi‐Gang She;Junyong Wang;Dating Sun;L. Shen;H. Xiang;Xu Cheng;Yan‐Xiao Ji;Yong-Ping Huang;Peng-Long Li;Xia Yang;Yanjie Cheng;Jun-Peng Ma;Haiping Wang;Yufeng Hu;Fengjiao Hu;S. Tian;Han Tian;Peng Zhang;Guang-Nian Zhao;Lin Wang;Manli Hu;Qin Yang;Lihua Zhu;Jingjing Cai;Juan Yang;Xin Zhang;Xinliang Ma;Qingbo Xu;R. Touyz;Peter P. Liu;R. Loomba;Yibin Wang;Hongliang Li
DOI:10.1016/j.jenvman.2023.117885
发表时间:2023-04-20
期刊:JOURNAL OF ENVIRONMENTAL MANAGEMENT
影响因子:8.7
作者:Zhang,Xingyuan;Tao,Jiayi;Li,Hongliang
通讯作者:Li,Hongliang
DOI:10.1186/s13020-023-00729-5
发表时间:2023-03-17
期刊:CHINESE MEDICINE
影响因子:4.9
作者:Tian, Ruifeng;Yang, Jinjie;Wang, Xiaoming;Liu, Shuaiyang;Dong, Ruixiang;Wang, Zhenya;Yang, Zifeng;Zhang, Yingping;Cai, Zhiwei;Yang, Hailong;Hu, Yufeng;She, Zhi-Gang;Li, Hongliang;Zhou, Junjie;Zhang, Xiao-Jing
通讯作者:Zhang, Xiao-Jing
A small molecule targeting ALOX12-ACC1 ameliorates nonalcoholic steatohepatitis in mice and macaques
DOI:10.1126/scitranslmed.abg8116
发表时间:2021-12
期刊:Science Translational Medicine
影响因子:17.1
作者:Xiao-Jing Zhang;Yan‐Xiao Ji;Xu Cheng;Yanjie Cheng;Hailong Yang;Junyong Wang;Ling‐Ping Zhao;Yong-Ping Huang;Dating Sun;Hui Xiang;L. Shen;Peng-Long Li;Jun-Peng Ma;Rui-Feng Tian;Juan Yang;Xinxin Yao;Haibo Xu;Rufang Liao;Li Xiao;Peng Zhang;Xin Zhang;Guang-Nian Zhao;Xi Wang;Manli Hu;S. Tian;Juan Wan;Jingjing Cai;Xinliang Ma;Qingbo Xu;Yibin Wang;R. Touyz;Peter P. Liu;R. Loomba;Zhi‐Gang She;Hongliang Li
通讯作者:Xiao-Jing Zhang;Yan‐Xiao Ji;Xu Cheng;Yanjie Cheng;Hailong Yang;Junyong Wang;Ling‐Ping Zhao;Yong-Ping Huang;Dating Sun;Hui Xiang;L. Shen;Peng-Long Li;Jun-Peng Ma;Rui-Feng Tian;Juan Yang;Xinxin Yao;Haibo Xu;Rufang Liao;Li Xiao;Peng Zhang;Xin Zhang;Guang-Nian Zhao;Xi Wang;Manli Hu;S. Tian;Juan Wan;Jingjing Cai;Xinliang Ma;Qingbo Xu;Yibin Wang;R. Touyz;Peter P. Liu;R. Loomba;Zhi‐Gang She;Hongliang Li
Pharmacological inhibition of arachidonate 12-lipoxygenase ameliorates myocardial ischemia-reperfusion injury in multiple species
花生四烯酸 12-脂氧合酶的药理抑制可改善多种物种的心肌缺血再灌注损伤。
DOI:10.1016/j.cmet.2021.08.014
发表时间:2021-10-05
期刊:CELL METABOLISM
影响因子:29
作者:Zhang, Xiao-Jing;Liu, Xiaolan;Li, Hongliang
通讯作者:Li, Hongliang
单加氧酶MOXD1调控非酒精性脂肪肝炎的作用及机制研究
- 批准号:82370585
- 项目类别:面上项目
- 资助金额:49万元
- 批准年份:2023
- 负责人:张晓晶
- 依托单位:
E3泛素连接酶TRIM26调控非酒精性脂肪肝炎的作用和分子机制研究
- 批准号:--
- 项目类别:面上项目
- 资助金额:55万元
- 批准年份:2021
- 负责人:张晓晶
- 依托单位:
国内基金
海外基金
