2. Academic Validation
  3. LncRNA-mRNA co-expression analysis reveals aquaporin-9-promoted neutrophil extracellular trap formation and inflammatory activation in sepsis

LncRNA-mRNA co-expression analysis reveals aquaporin-9-promoted neutrophil extracellular trap formation and inflammatory activation in sepsis

  • Int Immunopharmacol. 2024 Oct 25:140:112916. doi: 10.1016/j.intimp.2024.112916.
Pingping Liang 1,  Manman Zhu 2,  Xingzi Sun 3,  Li Wang 4,  Bin Li 5,  Siqi Ming 3,  Muhammad Younis 3,  Jianhua Yang 5,  Yongjian Wu 6,  Xi Huang 7
Affiliations

Affiliations

  • 1 Center for Infection and Immunity and Guangdong Provincial Engineering Research Center of Molecular Imaging, the Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong 519000, China; Guangdong-Hong Kong-Macao University Joint Laboratory of Interventional Medicine, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, Guangdong 519000, China; Key Laboratory of Traditional Chinese Medicine for the Prevention and Treatment of Infectious Diseases, Traditional Chinese Medicine Bureau of Guangdong Province, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, Guangdong 519000, China.
  • 2 Department of Clinical Laboratory, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, Guangdong 519000, China.
  • 3 Center for Infection and Immunity and Guangdong Provincial Engineering Research Center of Molecular Imaging, the Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong 519000, China.
  • 4 Department of Obstetrics and Gynecology, Perinatal Medical Center, the Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong 519000, China.
  • 5 MOE Key Laboratory of Gene Function and Regulation, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, Guangdong 510275, China.
  • 6 Center for Infection and Immunity and Guangdong Provincial Engineering Research Center of Molecular Imaging, the Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong 519000, China; Guangdong-Hong Kong-Macao University Joint Laboratory of Interventional Medicine, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, Guangdong 519000, China; Key Laboratory of Traditional Chinese Medicine for the Prevention and Treatment of Infectious Diseases, Traditional Chinese Medicine Bureau of Guangdong Province, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, Guangdong 519000, China. Electronic address: wuyj228@mail.sysu.edu.cn.
  • 7 Center for Infection and Immunity and Guangdong Provincial Engineering Research Center of Molecular Imaging, the Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong 519000, China; Guangdong-Hong Kong-Macao University Joint Laboratory of Interventional Medicine, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, Guangdong 519000, China; Key Laboratory of Traditional Chinese Medicine for the Prevention and Treatment of Infectious Diseases, Traditional Chinese Medicine Bureau of Guangdong Province, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, Guangdong 519000, China. Electronic address: huangxi6@mail.sysu.edu.cn.
PMID: 39133961 DOI: 10.1016/j.intimp.2024.112916
Abstract

Sepsis is a life-threatening condition caused by an excessive inflammatory response to an Infection. However, the precise regulatory mechanism of sepsis remains unclear. Using a strand-specific RNA-sequencing, we identified 115 hub differentially expressed long noncoding RNAs (lncRNAs) and 443 mRNAs in septic patients, primarily participated in crucial pathways including neutrophil extracellular trap (NET) formation and Toll-like Receptor signaling. Notably, NETs related gene aquaporin-9 (AQP9) and its associated lncRNAs exhibited significant upregulation in septic neutrophils. Functional experiments revealed AQP9 interacts with its lncRNAs to augment the formation of neutrophil NETs. In murine sepsis models, AQP9 inhibition with phloretin reduced proinflammatory cytokine production and lung damage. These findings provide crucial insights into the regulatory role of AQP9 in sepsis, unraveling its interaction with associated lncRNAs in transmitting downstream signals, holding promise in informing the development of novel therapeutic strategies aimed at ameliorating the debilitating effects of sepsis.

Keywords

AQP9; Inflammation; NETs; Neutrophil; Sepsis.

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