Department of Urology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China.
J Cell Mol Med. 2019 Nov;23(11):7268-7278. doi: 10.1111/jcmm.14555. Epub 2019 Sep 5.
Hyperoxaluria-induced calcium oxalate (CaOx) deposition is the key factor in kidney stone formation, for which adipose-derived stromal cells (ADSCs) have been used as a therapeutic treatment. Studies revealed that miR-20b-3p is down-regulated in hypercalciuric stone-forming rat kidney. To investigate whether ADSC-derived miR-20b-3p-enriched exosomes protect against kidney stones, an ethylene glycol (EG)-induced hyperoxaluria rat model and an in vitro model of oxalate-induced NRK-52E cells were established to explore the protective mechanism of miR-20b-3p. The results showed that miR-20b-3p levels were decreased following hyperoxaluria in the urine of patients and in kidney tissues from animal models. Furthermore, treatment with miR-20b-3p-enriched exosomes from ADSCs protected EG-induced hyperoxaluria rats, and cell experiments confirmed that co-culture with miR-20b-3p-enriched exosomes alleviated oxalate-induced cell autophagy and the inflammatory response by inhibiting ATG7 and TLR4. In conclusion, ADSC-derived miR-20b-3p-enriched exosomes protected against kidney stones by suppressing autophagy and inflammatory responses.
高草酸尿症诱导的草酸钙（CaOx）沉积是肾结石形成的关键因素，脂肪来源的基质细胞（ADSCs）已被用作治疗方法。研究表明，高钙尿结石形成大鼠肾脏中 miR-20b-3p 表达下调。为了研究 ADSC 来源的富含 miR-20b-3p 的外泌体是否对肾结石有保护作用，建立了乙二醇（EG）诱导的高草酸尿大鼠模型和草酸诱导的 NRK-52E 细胞体外模型，以探讨 miR-20b-3p 的保护机制。结果表明，高草酸尿症患者尿液和动物模型肾脏组织中 miR-20b-3p 水平降低。此外，ADSCs 来源的富含 miR-20b-3p 的外泌体治疗可保护 EG 诱导的高草酸尿大鼠，细胞实验证实，与富含 miR-20b-3p 的外泌体共培养可通过抑制 ATG7 和 TLR4 减轻草酸诱导的细胞自噬和炎症反应。综上所述，ADSC 来源的富含 miR-20b-3p 的外泌体通过抑制自噬和炎症反应来保护肾脏免受结石侵害。
