Inflammatory biomarkers and therapeutic potential of milk exosome-mediated CCL7 siRNA in murine intestinal ischemia-reperfusion injury

作者：Wendong Chen, Wenping Xu, Li Ma, Chun Bi, MeiXu Yang, Wei Yang · 发表于：Frontiers in Immunology · 年份：2025 · DOI：10.3389/fimmu.2024.1513196 · 被引用次数：6 · 研究领域：Extracellular vesicles in disease、RNA Interference and Gene Delivery、Endoplasmic Reticulum Stress and Disease

Background: Intestinal ischemia-reperfusion injury (IIRI) is a severe clinical condition associated with high morbidity and mortality. Despite advances in understanding the pathophysiology of IIRI, effective diagnostic and therapeutic strategies remain limited. Methods: Using transcriptome sequencing in a mouse model of IIRI, we identified potential biomarkers that were significantly upregulated in the IIRI group compared to the sham group. Based on these findings, we developed and evaluated a therapeutic strategy using milk-derived exosomes loaded with siRNA targeting CCL7 (M-Exo/siCCL7). Results: Focusing on Ccl7 as a hub gene, we explored the therapeutic efficacy of milk-derived exosomes loaded with siRNA targeting Ccl7 (M-Exo/siCCL7) in the IIRI model. M-Exo/siCCL7 treatment effectively attenuated intestinal inflammation and injury, as evidenced by reduced histological damage, decreased serum markers of intestinal barrier dysfunction, and attenuated systemic inflammation. Conclusion: Our findings provide new insights into the molecular mechanisms underlying IIRI, identify potential diagnostic biomarkers, and highlight the promise of exosome-based siRNA delivery as a novel therapeutic approach for IIRI.