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Abstract: TH-PO649

The Metabolic Syndrome Alters the Transcriptome and Proteome of Swine Mesenchymal Stem Cells

Session Information

Category: Development, Stem Cells, and Regenerative Medicine

  • 501 Development, Stem Cells, and Regenerative Medicine: Basic

Authors

  • Pawar, Aditya S., Mayo Clinic , Rochester, Minnesota, United States
  • Eirin, Alfonso, Mayo Clinic , Rochester, Minnesota, United States
  • Zhu, Xiang yang, Mayo Clinic , Rochester, Minnesota, United States
  • Lerman, Lilach O., Mayo Clinic , Rochester, Minnesota, United States
Background

Mesenchymal stem cells (MSCs) possess endogenous reparative properties & have been proposed as an exogenous therapeutic intervention in patients with chronic kidney disease (CKD). The metabolic syndrome (MetS) often coexists with and aggravates CKD, but whether MetS interferes with the reparative capacity of MSC remains unknown. We hypothesized that integrated comparison of the mRNA, microRNA, and protein content of MSCs isolated from Lean and MetS pigs would reveal pathways impacted in MSC by MetS.

Methods

Domestic pigs were fed a Lean or MetS diet (n=4 each) for 16 weeks. MSC were harvested from subcutaneous abdominal fat, and expression profiles of microRNAs, mRNAs, and proteins obtained by high throughput sequencing and LC-MS/MS proteomic analysis. TargetScan and ComiR were used to predict target genes of microRNAs (that often inhibit gene and protein expression) altered in MetS-MSCs. Functional annotation analysis was performed using DAVID 6.7 database.

Results

Differential expression analysis revealed 12 microRNAs upregulated in MetS-MSCs (fold change >1.4, p<0.05), which may target 7,728 genes, whereas 33 mRNAs and 78 proteins were downregulated (fold change <0.7, p<0.05). Integrated analysis showed that microRNAs upregulated in MetS-MSCs may target 33% of mRNAs and 45% of proteins downregulated in MetS-MSCs (Fig. 1A), and functional analysis showed that targeted proteins are mainly involved in apoptosis (e.g. CASP9, LAPTM5, LRG1) (Fig. 1B), angiogenesis (e.g. FGF1, AKT2) (Fig. 1C), and insulin signaling (e.g. AKT2, PP2CB) (Fig 1D).

Conclusion

MetS alters the transcriptome and proteome of swine adipose tissue-derived MSCs, via post-transcriptional regulation of genes and proteins involved in apoptosis, angiogenesis, and insulin signaling. MetS-induced changes in the MSC transcriptome and proteome may limit their use as an autologous cell-based regenerative therapy in CKD

Figure 1