Abstract: SA-PO452
Metabolic Syndrome (MetS) Upregulates the Tumour Necrosis Factor Alpha(TNF-α) Transcriptome and Proteome in Swine Adipose Tissue-Derived Mesenchymal Stem Cells (MSC)
Session Information
- Development and Regenerative Medicine
November 09, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Development, Stem Cells, and Regenerative Medicine
- 500 Development, Stem Cells, and Regenerative Medicine
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
- Afarideh, Mohsen, Mayo Clinic, Rochester, Minnesota, United States
- Lerman, Amir, Mayo Clinic, Rochester, Minnesota, United States
- Lerman, Lilach O., Mayo Clinic College of Medicine, Rochester, Minnesota, United States
Background
MSC have intrinsic reparative properties, & may serve as an exogenous therapeutic intervention in patients with chronic kidney disease (CKD). This microenvironment of MetS induces fat tissue inflammation, with upregulation of TNFα. MetS may also alter the transcriptome and proteome of adipose tissue-derived MSC, which might affect their reparative potency. We hypothesized that MetS upregulates MSC mRNA and proteins of the TNFα pathway.
Methods
Domestic pigs were fed a 16-week Lean or MetS diet (n=4 each), and MSC were then harvested from abdominal subcutaneous fat. Expression profiles of co-existing mRNAs and proteins in MSC were obtained by high-throughput sequencing and proteomics. DAVID 6.7 was used for functional annotation analysis to rank primary gene ontology categories for the mRNAs and proteins. Cellular location of the pro-inflammatory transcription factor nuclear factor (NF)-kB was evaluated by immunofluorescent staining.
Results
Differential expression after filtering for TNFα pathway genes revealed 13 mRNAs & 4 proteins upregulated in MetS compared to lean MSCs (fold change>1.4, p<0.05) (Fig. 1, A & B). Upregulated mRNAs were mostly involved in TNFα-1 receptor pathway. A similar pattern was observed in upregulated proteins, except for Traf2 involved in TNFα-2 receptor pathway. MetS induced changes in MSC TNFα signaling were associated with nuclear translocation of NF-kB(Fig 1, C).
Conclusion
MetS upregulates the TNFα transcriptome & proteome in swine adipose tissue-derived MSCs, leading to activation of NF-kB and inflammatory signaling. Hence, the MetS milieu may affect reparative function of endogenous MSC & limit their use as an exogenous regenerative therapy. Targeting the TNFα pathway might be a novel strategy to restore MSC expression patterns, & in turn function, and permit their use in subjects with MetS & CKD.