Abstract
Objectives To explore the effect of Oct-4 overexpressing mesenchymal stem cell derived extracellular vesicles (MSC-EVs) on acute kidney injury (AKI) and the related mechanism. Methods The renal tubular epithelial cells treated in low oxygen environment were cocultured with MSC-EVs and control medium for 48 hours. BrdU and TUNEL were used to assess cell proliferation and apoptosis. Mice with acute kidney injury were randomly divided into 4 groups, which were injected with Vehicle, EVs, Oct-4 overexpressing EVs (EVs + Oct-4) , and Oct-4 knocked-down EVs (EVs–Oct-4) . Blood creatinine and urine nitrone levels were assessed 48 hours after injection. The mice kedneys were harvested for TUNEL and PCNA staining to evaluate apoptosis and proliferation. Masson trichrome staining was used to evaluate renal fibrosis. Snail gene expression was assessed by PCR. The data was analyzed by ANOVA test and SNK-q test. Results 48 hours after hypoxic treatment, TUNEL showed the EVs + Oct-4 group has a lowest apoptosis level (0-1) / HPF. BrdU showed the EVs + Oct-4 group has a highest proliferation level (7±2) /HPF. Injection of Oct-4 overexpressing EVs could significantly decrease the level of blood Crea (28 mmol/ L) and BUN (17 mmol/L) , and the kidney fibrosis was also alleviated, as shown by slight Masson staining (3.2±1.0) ﹪ and few PCNA positive cells (70±7) /HPF 48 h post AKI, (21±4) /HPF 2 week post AKI) , the number of TUNEL positive cells was decreased (2±1) /HPF 48 h post AKI, (3±2) / HPF 2 week post AKI. PCR showed that Vehicle group had a highest Snail level 2.3±0.2, and the EVs + Oct-4 group had a lowest Snail level 0.7±0.1. Conclusions MSC-EVs provides therapeutic effects in ischemic-reperfusion injury. Oct-4 overexpression could enhance its therapeutic effects by inhibiting apoptosis, promoting proliferation, and inhibiting fibrosis. Key words: Acute kidney injury; Mesenchymal stem cells; Extracellular vesicles
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