ISSN 1006-298X      CN 32-1425/R

Chinese Journal of Nephrology, Dialysis & Transplantation ›› 2024, Vol. 33 ›› Issue (3): 207-214.DOI: 10.3969/j.issn.1006-298X.2024.03.002

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Protective effects of bone marrow mesenchymal stem cell exosomes on cisplatin-associated acute kidney injury

  

  • Online:2024-06-28 Published:2024-06-26

Abstract: Objective:To explore the role and mechanism of bone marrow mesenchymal stem cells-derived exosomes (BMSC-exos) in protecting against cisplatin (CDDP)-induced acute kidney injury (AKI).
Methodology:48 C57BL/6 mice were randomly divided into 4 groups: control (CN) group,cisplatin-induced AKI model (CDDP) group,CDDP+BMSC-exos (CDDP+EXO) group,and CDDP+EXO+PI3K inhibitor (LY294002) (CDDP+EXO+LY294002) group. Saline,cisplatin,cisplatin+BMSC-exos and cisplatin+BMSC-exos+LY294002 were injected intraperitoneally or Caudal vein,respectively. blood was retained for measurement of creatinine (SCr) and urea nitrogen (BUN); renal tissues were taken for pathological analyses; renal tubular epithelial cells (RTEC) were observed for apoptosis by TUNEL; and immunohistochemical staining was performed to detect Cleaved caspase-3,GRP-78,caspase-12 and CHOP expression localisation; Cleaved caspase-3,GRP-78,caspase-12,CHOP,PI3K and p-AKT expression were determined by Western Blot.
Results:In the CDDP-induced AKI model,the number of TUNEL-positive cells in renal tissues was significantly increased (P<0.05),and the area of immunohistochemically immunised Cleaved caspase-3,GRP-78,caspase-12 and CHOP positivity was significantly increased (P<0.05),and the Western Blot method confirmed the expression of Cleaved caspase-3,GRP-78,caspase-12 and CHOP expression levels were significantly up-regulated (P<0.05),and p-AKT expression levels were significantly down-regulated (P<0.05); the number of TUNEL-positive cells in renal tissues was significantly reduced by treatment with BMSC-exos (P<0.05),and the number of immunohistochemistry-immunoconjugated Cleaved caspase-3,GRP-78,caspase-12 and CHOP positive area was significantly reduced (P<0.05),Western Blot method confirmed that Cleaved caspase-3,GRP-78,caspase-12 and CHOP expression levels were significantly down-regulated (P<0.05),and the p-AKT expression level were significantly up-regulated (P<0.05); the number of TUNEL-positive cells in renal tissues was significantly increased (P<0.05),and the immunohistochemical immunoconjugate area of Cleaved caspase-3,GRP-78,caspase-12 and CHOP positivity was significantly increased (P<0.05) with the application of LY294002 prior to the treatment of BMSC-exos. Western Blot method confirmed that Cleaved caspase-3,GRP-78,caspase-12 and CHOP expression levels were significantly up-regulated (P<0.05) and p-AKT expression levels were significantly down-regulated (P<0.05).
Conclusion:The mechanism of CDDP-AKI protection by BMSC-exos may be achieved by inhibiting Endoplasmic reticulum stress and activating PI3K/Akt signalling pathway.


Key words: bone marrow mesenchymal stem cells, exosomes, cisplatinacute kidney injury, cell apoptosis