SEU research team published a paper in Science series
Recently, the team led by Prof. Liu Bicheng from Zhongda Hospital Southeast University published a research paper on Science Advances titled "Extracellular vesicle–encapsulated IL-10 as novel nanotherapeutics against ischemic AKI". This paper first reported on the novel nanotherapeutics for treating AKI by transporting IL-10 through extracellular vesicles. For this paper, both Prof. Liu Bicheng and Prof. Lyu Linli from Zhongda Hospital Southeast University are the corresponding authors, with Tang Taotao, a Ph.D. student, and Wang Bin, a physician-in-charge, as the co-first authors.
Part 01
Research Background
Acute kidney injury (AKI) is a commonly seen clinical syndrome, which is characterized by high mortality and morbidity rates and the possibility of turning into chronic kidney diseases, making itself an important public health issue in the world. And there has been no effective therapy clinically up to now. IL-10, as a kind of powerful anti-inflammatory factor, was shown in previous studies that it can significantly inhibit the production of pro-inflammatory factors and inflammatory cell infiltration in a variety of kidney disease models, indicating its vital potential application prospects in the anti-inflammatory treatment of kidney diseases.
Part 02
Research Process and Progress
Extracellular Vesicles (EV), with a bilayer lipid membrane structure secreted by living cells, is a naturally stable nanoscale membrane vesicle highlighting sound stability, biological compatibility, low immunogenicity, and no cytotoxicity, thus providing a new drug administration strategy for the treatment of diseases. The research team have interfered with RAW macrophages through plasmid transfection and dexamethasone and successfully enriched the released EV with IL-10 (IL-10+ EV). Compared with the free form, entrapped EV can significantly improve the stability of IL-10 to protect it from degradation. Meanwhile, LC-MS/MS analysis revealed that IL-10+ EV is rich in integrin molecules, including ITG α4β1, α5β1, αLβ2 and αMβ2. Given these integrins, IL-10+ EV, abundant in ischemia/ reperfusion (I/R) induced injured kidney, can be ingested by renal tubular epithelial cells and macrophages. Therefore, the delivery of macrophage-derived extracellular vesicles has not only improved the stability of IL-10, but also enhanced its ability of target damage to kidney.
In animal models, IL-10+EV can significantly improve I/R-induced AKI, protect renal function and alleviate tubular damage. The mechanism research has found that IL-10+ EV can reduce tubular cell damage by inhibiting the activation of mTOR signal pathway, thus increasing TEC mitochondrion autophagy level and maintaining the morphology and functional homeostasis of mitochondrion, which include reducing the ROS production of mitochondrion, and improving the respiratory function and membrane potential of mitochondrion. In addition, IL-10+ EV can also induce the transformation of interstitial macrophages into M2-type cells, promoting the repair of renal damage. Meanwhile, IL-10+ EV also showed favorable therapeutic effects in damage model of mouse with cisplatin-induced AKI. Furthermore, the research team have also investigated whether IL-10+ EV inhibits AKI's progression to chronic kidney disease (CKD). It is inspiring to learn that, at 4 weeks after I/R injury, early treatment of IL-10+ EV can dramatically reduce renal pathological damage and renal fibrosis to inhibit extracellular matrix accumulation and inflammatory cell infiltration, suggesting that this therapy can be used to prevent the transformation of AKI into CKD.
Part 03
Research Significance
This study has successfully created IL-10+ EV targeting nano drugs with high stability and good renal targeting. Besides, the study also clarified the mechanism of AKI treatment with IL-10+ EV, that is, the transformation of macrophage M2 was induced by maintaining the function homeostasis of TEC mitochondrion to promote the repair of renal injury, thus providing experimental and theoretical evidence for the subsequent clinical translation of IL-10+ EV.
Submitted by: Zhongda Hospital Southeast University
Translated by Melody Zhang
Revised by Chen Xuerong
Proofread by Eric Song, Melody Zhang
Edited by Luo Xinyi
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