The urinary exosomes derived from premature infants attenuate cisplatin-induced acute kidney injury in mice via microRNA-30a-5p/ mitogen-activated protein kinase 8 (MAPK8)
Autor: | Mingming Ma, Qiao Luo, Lijing Fan, Weilong Li, Qiang Li, Yu Meng, Chen Yun, Hongwei Wu, Yongping Lu, Shuang Cui, Fanna Liu, Bo Hu, Baozhang Guan, Huanhuan Liu, Shengling Huang, Wenxue Liang, Stanislao Morgera, Bernhard Krämer, Shaodong Luan, Lianghong Yin, Berthold Hocher |
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Jazyk: | angličtina |
Rok vydání: | 2022 |
Předmět: |
Down-Regulation
Bioengineering Exosomes Applied Microbiology and Biotechnology Cell Line Mice Animals Humans Urinary exosomes microRNA-30a-5p mitogen-activated protein kinase 8 Infant Newborn General Medicine Mice Inbred C57BL Disease Models Animal MicroRNAs HEK293 Cells acute kidney injury Creatinine Female Chemical and Drug Induced Liver Injury Cisplatin TP248.13-248.65 Infant Premature Biotechnology Research Article Research Paper |
Zdroj: | Bioengineered article-version (VoR) Version of Record Bioengineered, Vol 13, Iss 1, Pp 1650-1665 (2022) |
ISSN: | 2165-5987 2165-5979 |
Popis: | Acute kidney injury (AKI) is a susceptible factor for chronic kidney disease (CKD). There is still a lack of effective prevention methods in clinical practice. This study investigated the protective effect of the urinary exosomes from premature infants on cisplatin-induced acute kidney injury. Here we isolated exosomes from the fresh urine of premature infants. A C57BL/6 mice model of cisplatin-induced acute kidney injury was given 100 ug urinary exosomes 24 hours after model establishment. The kidneys were collected for pathological examination and the evaluation of renal tubular damage and apoptosis. In the in vitro experiment, human renal cortex/proximal tubular cells (HK-2) were induced by cisplatin to assess the effect of the urine exosomes from premature infants. Exosome microRNA (miRNA) sequencing technology was applied to investigate the miRNAs enriched in exosomes and the dual-luciferase gene reporter system to examine the targeting relationship of the miRNA with target genes. The results indicated that the urinary exosomes could decrease the serum creatinine level and the apoptosis of renal tubular cells, and reduce mice mortality. In addition, miR-30a-5p was the most abundant miRNA in the exosomes. It protected HK-2 cells from cisplatin-induced apoptosis by targeting and down-regulating the mitogen-activated protein kinase 8 (MAPK8). Together, our findings identified that the urinary exosomes derived from premature infants alleviated cisplatin-induced acute kidney injury and inhibited the apoptosis of HK-2 via miR-30a-5p, which could target MAPK8. These findings implied that urinary exosomes from premature infants riched in miR-30a-5p might become a potential treatment for AKI. |
Databáze: | OpenAIRE |
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