Abstract 586: Hydroxycholesterol or Cyclic AMP Upregulates the Expression of Renin in Human Mesenchymal Stem Cells
Renin is a key enzyme in the renin-angiotensin system which plays a vital role in the regulation of cardiovascular homeostasis. Metanephric mesenchymal cells are assumed to be the origin of vascular smooth muscle cells and of renin precursor cells. It is also suggested that renin precursor cells are metaplastically modified smooth muscle cells and/or precursor of smooth muscle cells during ontogeny. However, there is no direct evidence that mesenchymal stem cells (MSCs) can be induced to become renin expressing cells. Previously we have reported that the nuclear hormone receptor liver X receptor (LXR) is a major transcriptional regulator of renin gene expression. In this study we examined the effect of LXR agonists on renin gene expression in human mesenchymal stem cells.
Methods: Human mesencymal stem cells were subjected to serum starvation for 16 hours. We then added the LXR natural ligand 22-hydroxycholesterol (10-7 M) and investigated mRNA expression of renin and ATP-binding cassette transporter A1 (ABCA1) which is well known upregulated by LXR activation after 6 hours of pharmacological treatment by using real-time RT-PCR. We further examined the renin and ABCA1 mRNA expression by adding cyclic AMP (10-3 M).
Results: Human MSCs treated with 22-hydroxycholesterol exhibited an increase in expression of renin (1.7 ± 0.3 fold change for MSCs without treatment, P < 0.05). There was an increase in ABCA1 expression (1.6 ± 0.1 fold change, P < 0.05), suggesting that 22-hydroxycholesterol effectively acted as a LXR ligand. Furthermore, cyclic AMP showed also upregulated renin and ABCA1 mRNA expression (2.2 ± 0.3 and 1.9 ± 0.1 fold changes for MSCs without treatment, respectively, P < 0.05).
Conclusion: Our results suggest that the activation of liver X receptor upregulates renin mRNA expression in human mesenchymal stem cells and suggest that these cells may be the origin of renin cells during embryonic development. Our observations provide insight into possible novel understanding of the renin-angiotensin system (RAS) and RAS related cardiovascular disease.