Mesenchymal stromal cells (MSC) have been shown to attenuate renal ischemia/reperfusion (I/R) injury in rodents. Still, the mechanisms of such a nephroprotection remain unclear. Here, rats were intravenously infused with MSC (1.5x10^6 cells in 1 ml saline; MSCD-7 group, n=6) or equivalent volume of saline (SD-7 group, n=6) 7 days before kidney sampling. High-throughput RNA sequencing technology was used to compare transcriptomic renal profiles, using TopHat and Cufflinks open-source software tools. A total of 494 and 256 genes were found to be significantly (q-value <.05) down- and up-regulated in mscd-7 versus sd-7 groups, respectively. Hierarchical cluster analysis by “david” “webgestalt” softwares highlighted that the metabolic pathways mostly affected msc included adipogenesis, insulin signalling, fatty acid (fa) biosynthesis, il-6 b-cell receptor il-3 pathway nuclear receptors involved lipid me- tabolism. Real-time qpcr immunoblotting analyses confirmed pivotal enzymes of fa biosynthesis were significantly downregulated group, whereas expression ppar alpha, a transcription factor oxidation, was induced msc. Additional- ly, fat />CD36 – a key regulator of membrane uptake of FA – was increased in MSCD-7 kidneys, with a preferential localization in proximal tubules (PT). As a whole, our data suggest that MSC infusion causes critical modifications of lipid metabolism, including (i) down-regulation of FA biosynthesis; (ii) activation of PPAR alpha pathway, and (iii) prioritization of FA as sources of energy in PT cells, which may eventually prevent lipid peroxidation and attenuate renal I/R damage.
نوع الوثيقة:
conferencePaper
اللغة:
English
العلاقة:
24th Annual Meeting, Bruxelles, Belgium (du 16 au 17 Mars 2017)
