Lnc-PINK regulation of innate immunity in lung epithelial cells

Lnc-PINK对肺上皮细胞先天免疫的调节

• 批准号: 10365976
• 负责人: LIN LIU
• 金额: $ 18.7万
• 依托单位: OKLAHOMA STATE UNIVERSITY STILLWATER
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-03-05 至 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10365976
• 关键词: Acute Respiratory Distress Syndrome; Antiviral Agents; Cell physiology; Data; Development; Drug Targeting; Epidemic; Epithelial; Epithelial Cells; Gene Expression; Goals; Host Defense; Human; Inflammasome; Integration Host Factors; Lung; Mediating; Messenger RNA; Modeling; Molecular; Molecular Cloning; Mutation; Natural Immunity; Nucleotides; PINK1 gene; Periodicity; Pharmacology; Pneumonia; Proteins; Regulation; Respiratory System; Role; TXNIP gene; Testing; Therapeutic Intervention; Transcript; Untranslated RNA; Viral; Viral Drug Resistance; Viral Proteins; Viral Vaccines; base; defense response; first responder; influenza infection; influenzavirus; mortality; novel; pandemic disease; respiratory infection virus; respiratory pathogen; respiratory virus; transcriptome sequencing

PROJECT SUMMARY The influenza virus infects the respiratory tract and may result in acute respiratory distress syndrome and pneumonia associated with a high mortality rate. The long-term goal of this project is to understand the molecular mechanisms how the lung epithelial cells responds to and restricts respiratory virus infection. Innate immunity is the first responder to respiratory pathogen invasion and provides the first line of defense in the lung. Thus enhancing the host defense response against respiratory virus by targeting lung epithelial host factors is a strategy to restrict respiratory virus infection regardless of any viral changes. Long non-coding RNAs (lncRNAs) are mRNA-like transcripts with a size of > 200 nucleotides, but that do not encode proteins and are involved in diverse cellular processes including innate immunity. Through RNA sequencing analysis and molecular cloning, we have identified a novel lncRNA transcript, lnc-PINK1-2:5 in lung epithelial cells that reduces influenza virus infection and up-regulates the expression of thioredoxin interacting protein (TXNIP) that activates NLRP3 inflammasomses. Based on this preliminary data, we hypothesized that lnc-PINK1-2:5 restricts respiratory virus infection by activating NLRP3 inflammasomes via upregulating TXNIP gene expression in lung epithelial cells. Aim I will establish the functional roles of lnc-PINK1-2:5 in influenza virus infection of human lung epithelial cells. Aim II will delineate the molecular mechanisms of lnc-PINK1-2:5- mediated restriction of influenza virus in human lung epithelial cells.

项目总结

项目成果

MicroRNA-9-1 Attenuates Influenza A Virus Replication via Targeting Tankyrase 1.

• DOI: 10.1159/000532063
• 发表时间: 2023
• 期刊: Journal of innate immunity
• 影响因子: 5.3

SNHG15 aids SARS-CoV-2 entry via RABL2A.

• DOI: 10.1080/15476286.2023.2241755
• 发表时间: 2023-01
• 期刊: RNA BIOLOGY
• 影响因子: 4.1
• 作者: Pushparaj, Samuel;Gandikota, Chaitanya;Vaddadi, Kishore;Liang, Yurong;Liu, Lin
• 通讯作者: Liu, Lin

Regulation of influenza A virus infection by Lnc-PINK1-2:5.

• DOI: 10.1111/jcmm.17249
• 发表时间: 2022-04
• 期刊: Journal of cellular and molecular medicine
• 影响因子: 5.3
• 作者: Pushparaj S;Zhu Z;Huang C;More S;Liang Y;Lin K;Vaddadi K;Liu L
• 通讯作者: Liu L

Axin1: A novel scaffold protein joins the antiviral network of interferon.

• DOI: 10.1111/mmi.14995
• 发表时间: 2022-12
• 期刊: MOLECULAR MICROBIOLOGY
• 影响因子: 3.6
• 作者: Guo, Yujie;Bamunuarachchi, Gayan;Vaddadi, Kishore;Zhu, Zhengyu;Gandikota, Chaitanya;Ahmed, Kainat;Pushparaj, Samuel;More, Sunil;Xiao, Xiao;Yang, Xiaoyun;Liang, Yurong;Mukherjee, Sanjay;Baviskar, Pradyumna;Huang, Chaoqun;Li, Shitao;Oomens, Antonius G. P.;Metcalf, Jordan Patrick;Liu, Lin
• 通讯作者: Liu, Lin