2. Academic Validation
  3. Identification of inflammation related lncRNAs and Gm33647 as a potential regulator in septic acute lung injury

Identification of inflammation related lncRNAs and Gm33647 as a potential regulator in septic acute lung injury

  • Life Sci. 2021 Oct 1;282:119814. doi: 10.1016/j.lfs.2021.119814.
Liying Zou 1,  Qing Yu 1,  Luyun Zhang 1,  Xiu Yuan 1,  Fang Fang 1,  Feng Xu 2
Affiliations

Affiliations

  • 1 Department of Critical Care Medicine, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders (Chongqing), China International Science and Technology Cooperation Base of Child development and Critical Disorders, Children's Hospital of Chongqing Medical University, Chongqing, PR China.
  • 2 Department of Critical Care Medicine, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders (Chongqing), China International Science and Technology Cooperation Base of Child development and Critical Disorders, Children's Hospital of Chongqing Medical University, Chongqing, PR China. Electronic address: [email protected].
PMID: 34298039 DOI: 10.1016/j.lfs.2021.119814
Abstract

Sepsis is commonly complicated by acute lung injury (ALI). We aimed to determine the long non-coding RNAs (lncRNAs) and mRNAs expression profiles. Septic acute lung injury mouse model was established by cecal ligation and puncture. LPS was applied to induce inflammation in mouse alveolar macrophages (MH-s). Besides, LPS/Nigericin sodium salt was used to activate inflammasome in MH-s. LncRNA and mRNA profiles were detected using an Agilent microarray and identified by qPCR. Bioinformatic analyses were employed to analyze the expression profiles and multiple biological functions. Inflammation-related mRNAs were selected according to KEGG pathways and GO terms including inflammation response, immune response and cytokine activity. A network of inflammation related mRNAs and co-expressed lncRNAs was conducted. Finally, Gm33647 was identified as potential regulator in septic acute lung injury. Gm33647 was knock-downed via siRNA to explore functions. The results showed 353 differentially expressed lncRNAs and 3116 differentially expressed mRNAs were identified. Co-expression networks of lncRNA-mRNA showed Gm33647 was a hub gene. Cis- and trans-regulation analyses revealed Gm41442, Gm38850 and Gm36841 could function as a network in septic ALI. LncRNA Gm33647 was reduced by LPS and increased by inflammasome activation in MH-s. Silencing Gm33647 up-regulated IL-6, IL10 and TNF-α in MH-s. When inflammasome was activated by LPS/Nigericin sodium salt, IL-1β, IL-18 and Caspase 1 were increased by silencing Gm33647 in MH-s. These results identified inflammation related lncRNAs and Gm33647 as potential regulators in septic ALI.

Keywords

ALI; Inflammation; Long non-coding RNAs; Microarray; Sepsis.

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