Human umbilical cord blood mononuclear cells protect against renal tubulointerstitial fibrosis in cisplatin-treated rats - 30/11/19
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Graphical abstract |
Highlights |
• | We establish a new, fast, stable and repeatable model of renal interstitial fibrosis after CP-induced AKI in rats. |
• | hUCBMNCs may have protective effects on renal interstitial fibrosis after CP-induced AKI in rats. |
• | The protective effects may be related to anti-inflammation, anti-oxidation, inhibiting cleaved-Caspase 3 of renal tissues. |
• | hUCBMNCs transplantation may provide a new prevention strategy for tubulointerstitial fibrosis after cisplatin-induced AKI. |
Abstract |
Currently, there is no effective method to prevent renal interstitial fibrosis after acute kidney injury (AKI). In this study, we established and screened a new renal interstitial fibrosis rat model after cisplatin-induced AKI. Our results indicated that rats injected with 4 mg/kg cisplatin once a week for two weeks after firstly administrated with 6.5 mg/kg loading dose of cisplatin could set up a more accurate model reflecting AKI progression to renal interstitial fibrosis. Then, we investigated the effects and possible mechanisms of human umbilical cord blood mononuclear cells (hUCBMNCs) on renal tubular interstitial fibrosis after cisplatin-induced AKI. In rats injected with hUCBMNCs for four times, level of matrix metalloproteinase 7 (MMP-7) in serum and urine, urinary albumin/creatinine ratio, tubular pathological scores, the relative collagen area of the tubulointerstitial region, endoplasmic reticulum dilation and the mitochondrial ultrastructural damage were significantly improved. The level of reactive oxygen species, α-smooth muscle actin (α-SMA), [NOD]-like pyrin domain containing protein 3 and cleaved-Caspase 3 in renal tissue decreased significantly. However, in rats injected with hUCBMNCs for two times, no significant difference was discovered in MMP-7 levels and urinary albumin/creatinine ratio. Although expression of α-SMA and the percentage areas of collagen staining in tubulointerstitial tissues were ameliorated in rats injected with hUCBMNCs for two times, the effects were significantly weaker than those in rats injected with hUCBMNCs for four times. Taken together, our study constructed a highly efficient, duplicable novel rat model of renal fibrosis after cisplatin-induced AKI. Multiple injections of hUCBMNCs may prevent renal interstitial fibrosis after cisplatin-induced AKI.
Le texte complet de cet article est disponible en PDF.Keywords : Acute kidney injury, Chronic kidney disease, Cisplatin, Human umbilical cord blood mononuclear cells, Renal interstitial fibrosis
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