MiR-625-5p is a potential therapeutic target in sepsis by regulating CXCL16/CXCR6 axis and endothelial barrier

  • Int Immunopharmacol. 2024 Jun 17:137:112508. doi: 10.1016/j.intimp.2024.112508.
Xiao Huang  1 ,  Yuxin Fei  1 ,  Xiaoyu Qiu  2 ,  Tiantian Qian  3 ,  Quanmei Shang  1 ,  Jinfeng Cui  1 ,  Yutong Song  1 ,  Shurui Sheng  1 ,  Wenhan Xiao  1 ,  Qilin Yu  1 ,  Tao Wang  4 ,  Xiaozhi Wang  5
Affiliations
  • 1. Department of Intensive Care Unit, Binzhou Medical University Hospital, Binzhou, Shandong, China.
  • 2. Department of Intensive Care Unit, Binzhou Medical University Hospital, Binzhou, Shandong, China; Department of Pulmonary and Critical Care Medicine, Yantai Yuhuangding Hospital, Yantai, Shandong, China.
  • 3. Department of Respiratory Medicine, Ji'nan Zhangqiu District People's Hospital, No. 1920 Mingshuihuiquan Road, Ji'nan, 250200, Shandong, China.
  • 4. Department of Intensive Care Unit, Binzhou Medical University Hospital, Binzhou, Shandong, China. Electronic address: [email protected].
  • 5. Department of Intensive Care Unit, Binzhou Medical University Hospital, Binzhou, Shandong, China. Electronic address: [email protected].
PMID: 38889512 DOI: 10.1016/j.intimp.2024.112508
Abstract

Background: MicroRNA plays an important role in the progression of Sepsis. We found a significant increase of in miR-625-5p expression in the blood of patients with Sepsis, and lipopolysaccharide (LPS)-stimulated EA.hy926 cells. To date, little is known about the specific biological function of miR-625-5p in Sepsis.

Methods: Changes in miR-625-5p expression were verified through quantitative real-time polymerase chain reaction in 45 patients with Sepsis or septic shock and 30 healthy subjects. In vitro, EA.hy926 cells were treated with LPS. Transendothelial electrical resistance assay and FITC-dextran were used in evaluating endothelial barrier function.

Results: Herein, patients with Sepsis or septic shock had significantly higher miR-625-5p expression levels, chemokine (C-X-C motif) ligand 16 (CXCL16) levels, and glycocalyx components than the healthy controls, and miR-625-5p level was positively correlated with disease. Kaplan-Meier analysis demonstrated a strong association between miR-625-5p level and 28-day mortality. Furthermore, the miR-625-5p inhibitor significantly alleviated LPS-induced endothelial barrier injury in vitro. Then, miR-625-5p positively regulated CXCL16 and down-regulated miR-625-5p attenuated CXCL16 transcription and expression in EA.hy926 cells. CXCL16 knockout significantly alleviated vascular barrier dysfunction in the LPS-induced EA.hy926 cells. sCXCL16 treatment in EA.hy926 cells significantly increased endothelial hyperpermeability by disrupting endothelial glycocalyx, tight junction proteins, and adherens junction proteins through the modulation of C-X-C Chemokine Receptor type 6 (CXCR6).

Conclusions: Increase in miR-625-5p level may be an effective biomarker for predicting 28-day mortality in patients with Sepsis/septic shock. miR-625-5p is a critical pathogenic factor for endothelial barrier dysfunction in LPS-induced EA.hy926 cells because it activates the CXCL16/CXCR6 axis.

Keywords
CXCL16; CXCR6; Endothelial barrier; Sepsis; miR-625-5p.
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