[en] Background: Mesenchymal stromal cells (MSC) have been demonstrated to attenuate renal ischemia/reperfusion (I/R) damage in rodents. The mecha- nisms of such nephroprotection remain unclear.
Materials and Methods: Male Lewis rats aged of 8–10 weeks received tail i.v injection of 1.5x106 MSC in 1 mL saline (MSCD-7, n = 11) or saline alone (SD- 7, n = 6) 7 days before renal I/R. Left renal ischemia (by clamping the renal pedicle) lasted 45 min. Right nephrectomy was simultaneously performed. Blood sample was collected from inferior vena cava 48 h post reperfusion. Renal function was assessed by measuring serum creatinine (SCr) levels. Expressions of inflammatory and apoptotic markers by real-time (RT)-qPCR were comparatively quantified. High-throughput RNA sequencing was applied to MSCD-7 vs. SD-7 non-ischemic right kidneys. Relevant pathways were detected using an Over-Representation Analysis with WebGestalt, and confirmed by RT-qPCR.
Results: Scr levels reached 1.4 ` 0.7 vs. 2.4 ` 0.8 mg/dL in MSCD-7 vs. SD-7 group (p < 0.05). MSC infusion significantly reduced mRNA expression of Casp3, Hsp 70, Kim-1, Mcp-1 and Il-6 and increased mRNA expression of Bcl compared to saline. Among 25 908 genes, 748 were identified as significantly differentially expressed (False Discovery Rate (FDR), <0.05) between MSCD-7 and SD-7 non-ischemic kidneys. Among the most affected metabolic pathways, renal lipid metabolism was significantly altered, with down-regulation of fatty acid biosynthesis and an up-regulation of PPARa pathway in MSCD-7 vs. SD-7 groups. By immunoblotting, PPARa and phosphorylated-PPARa were significantly increased in MSCD-7 vs. SD-7 kidneys, in both non-ischemic and ischemic conditions. Moreover, levels of malondialdehyde-derived lipid peroxidation products were decreased in MSCD-7 ischemic kidneys in comparison to SD-7 ischemic kidneys. Conclusion: MSC infusion at day 7 prior injury critically impacts renal lipid metabolism, which may condition kidney parenchyma against I/R.
Disciplines :
Urology & nephrology Surgery
Author, co-author :
ERPICUM, Pauline ; Centre Hospitalier Universitaire de Liège - CHU > Service de néphrologie
Rowart, Pascal ; Université de Liège - ULiège > Département des sciences cliniques > Néphrologie
POMA, Laurence ; Centre Hospitalier Universitaire de Liège - CHU > Service de néphrologie
KRZESINSKI, Jean-Marie ; Centre Hospitalier Universitaire de Liège - CHU > Service de néphrologie
DETRY, Olivier ; Centre Hospitalier Universitaire de Liège - CHU > Chirurgie abdo, sénologique, endocrine et de transplantation
JOURET, François ; Centre Hospitalier Universitaire de Liège - CHU > Service de néphrologie
Language :
English
Title :
Administration of mesenchymal stromal cells before renal ischemia/reperfusion attenuates kidney injury and modulates renal lipid metabolism in rats
Publication date :
September 2017
Event name :
18th Congress
Event organizer :
European Society for Organ Transplantation (ESOT)
Event place :
Barcelona, Spain
Event date :
Du 24 au 27 septembre 2017
Audience :
International
Journal title :
Transplant International
ISSN :
0934-0874
eISSN :
1432-2277
Publisher :
Springer International, Heidelberg, Germany
Special issue title :
Abstracts of the 18th Congress of the European Society for Organ Transplantation
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