Yea Ji-Hye, Yoon Yeo Min, Lee Jun Hee, Yun Chul Won, Lee Sang Hun
Medical Science Research Institute, Soonchunhyang University Seoul Hospital, Seoul, Republic of Korea.
Institute of Tissue Regeneration Engineering, Dankook University, Cheonan, Republic of Korea.
J Tissue Eng. 2021 Nov 29;12:20417314211059624. doi: 10.1177/20417314211059624. eCollection 2021 Jan-Dec.
Chronic kidney disease (CKD) is defined as structural and functional abnormalities of the kidney due to inflammation and fibrosis. We investigated the therapeutic effects of exosomes secreted by melatonin-stimulated mesenchymal stem cells (Exocue) on the functional recovery of the kidney in a CKD mouse model. Exocue upregulated gene expression of micro RNAs (miRNAs) associated with anti-inflammatory and anti-fibrotic effects. Exocue-treated groups exhibited low tumor necrosis factor-α and transforming growth factor-β levels in serum and fibrosis inhibition in kidney tissues mediated through regulation of cell apoptosis and proliferation of fibrosis-related cells. Exocue treatment decreased the gene expression of CKD progression-related miRNAs. Moreover, the CKD severity was alleviated in the Exocue group via upregulation of aquaporin 2 and 5 levels and reduction of blood urea nitrogen and creatinine, resulting in functional recovery of the kidney. In conclusion, Exocue could be a novel therapeutic agent for treating CKD by regulating inflammation and fibrosis.
慢性肾脏病（CKD）被定义为由于炎症和纤维化导致的肾脏结构和功能异常。我们在CKD小鼠模型中研究了褪黑素刺激的间充质干细胞分泌的外泌体（Exocue）对肾脏功能恢复的治疗作用。Exocue上调了与抗炎和抗纤维化作用相关的微小RNA（miRNA）的基因表达。Exocue治疗组血清中肿瘤坏死因子-α和转化生长因子-β水平较低，并且通过调节细胞凋亡和纤维化相关细胞的增殖介导肾脏组织中的纤维化抑制。Exocue治疗降低了与CKD进展相关的miRNA的基因表达。此外，Exocue组通过上调水通道蛋白2和5的水平以及降低血尿素氮和肌酐减轻了CKD的严重程度，从而导致肾脏功能恢复。总之，Exocue可能是一种通过调节炎症和纤维化来治疗CKD的新型治疗剂。
