Accelerating corneal wound healing using exosome-mediated targeting of NF-κB c-Rel.

IF 5 3区 医学 Q2 IMMUNOLOGY
Wenbo Zhao, Xiaozhen He, Ruiling Liu, Qingguo Ruan
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引用次数: 2

Abstract

The integrity of the corneal epithelium is essential for the maintenance of the physiological function of the cornea. Studies have found that inflammation greatly delays corneal wound healing. NF-κB c-Rel is preferentially expressed by immune cells and promotes the expression of inflammatory cytokines. In the current study, we sought to investigate whether c-Rel could be used as a potential therapeutic target for treating a corneal injury. Our studies reveal that expressions of c-Rel and its inflammatory targets are significantly increased in the cornea of mice with corneal injury. In addition, we find that c-Rel-deficient mice exhibit accelerated corneal wound healing and reduced expression of inflammatory cytokines. Further studies show that topical treatment on the corneal surface using nano-polymers or exosomes loaded with c-Rel-specific siRNA (siRel) can effectively accelerate regular and diabetic corneal wound healing. More importantly, we find that exosomes, as carriers of siRel, showed better efficacy than nano-polymers in treating corneal injury. We further demonstrate that exosomes secreted by mesenchymal stem cells can efficiently transfer siRNA into macrophages and dendritic cells but not T cells. Taken together, these results indicate that blocking c-Rel may represent an attracting strategy for the treatment of both regular and diabetic corneal injury.

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外泌体介导的NF-κB c-Rel靶向加速角膜创面愈合。
角膜上皮的完整性对维持角膜的生理功能至关重要。研究发现,炎症极大地延缓了角膜伤口的愈合。NF-κB c-Rel在免疫细胞中优先表达,促进炎症细胞因子的表达。在目前的研究中,我们试图研究c-Rel是否可以作为治疗角膜损伤的潜在治疗靶点。我们的研究发现,在角膜损伤小鼠的角膜中,c-Rel及其炎症靶点的表达显著增加。此外,我们发现c- rel缺陷小鼠表现出角膜伤口愈合加速和炎症细胞因子表达减少。进一步的研究表明,使用纳米聚合物或负载c- rel特异性siRNA (siRel)的外泌体在角膜表面局部治疗可以有效地加速常规和糖尿病角膜伤口愈合。更重要的是,我们发现外泌体作为siRel的载体,在治疗角膜损伤方面表现出比纳米聚合物更好的效果。我们进一步证明,间充质干细胞分泌的外泌体可以有效地将siRNA转移到巨噬细胞和树突状细胞中,但不能转移到T细胞中。综上所述,这些结果表明,阻断c-Rel可能是治疗常规和糖尿病性角膜损伤的一种有吸引力的策略。
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来源期刊
CiteScore
11.10
自引率
1.20%
发文量
45
审稿时长
11 weeks
期刊介绍: Inflammation and Regeneration is the official journal of the Japanese Society of Inflammation and Regeneration (JSIR). This journal provides an open access forum which covers a wide range of scientific topics in the basic and clinical researches on inflammation and regenerative medicine. It also covers investigations of infectious diseases, including COVID-19 and other emerging infectious diseases, which involve the inflammatory responses. Inflammation and Regeneration publishes papers in the following categories: research article, note, rapid communication, case report, review and clinical drug evaluation.
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