Identification of molecular pathways and protein-protein interactions in adipose tissue-derived mesenchymal stromal cells (ASCs) under physiological oxygen concentration in a diabetic rat model

在糖尿病大鼠模型中,在生理氧浓度下脂肪组织来源的间充质基质细胞 (ASC) 中的分子通路和蛋白质-蛋白质相互作用的鉴定

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作者:Luis-Miguel Paco-Meza, MDolores Carmona, Sagrario Cañadillas, Ana Lopez-Diaz, Francisco Muñoz-López, Alvaro Jimenez-Arranz, Ipek Guler, Concha Herrera

Conclusion

These results provide valuable information about gene pathways and underlying molecular mechanisms by which diabetes disturbs ASCs biology in physiological oxygen conditions. Furthermore, they reveal, molecular targets to improve the use of ASCs in autologous transplantation.

Methods

ASCs derived from healthy (ASCs-C) and diabetic (ASCs-D) rats were expanded under standard culture conditions (21% O2) or cultured in physiological oxygen conditions (3% O2) and characterized. Differential gene expressions (DEGs) of ASCs-D with respect to ASCs-C were identified and analyzed with bioinformatic tools. Protein-protein interaction (PPI) networks, from up- and down-regulated DEGs, were also constructed.

Results

The bioinformatic analysis revealed 1354 up-regulated and 859 down-regulated DEGs in ASCs-D, with 21 and 78 terms over and under-represented, respectively. Terms linked with glycosylation and ribosomes were over-represented and terms related to the activity of RNA-polymerase II and transcription regulation were under-represented. PPI network disclosed RPL11-RPS5 and KDR-VEGFA as the main interactions from up- and down-regulated DEGs, respectively.

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