Abstract 13931: Effects of PGE2 on Renal CD44+ Mesenchymal Stem Cell (CD44+ MSC) Migration
Background: Recent studies have identified a reservoir of stem and progenitor cells in the adult kidney. However, the significance of these observations for renal function remains unclear. Our laboratory has shown that CD44+ MSCs exist in the adult kidney and that that under Low Salt/Captopril stimulation in vivo, these cells migrate to the JG area and differentiate to renin expressing cells along the JG cell lineage, contributing to JG hyperplasia. The mechanisms governing these decisions are still elusive. It has been shown that macula densa (MD) cells in the kidney can regulate renin secretion via the release of prostanoids. Here we hypothesized that PGE2 and PGI2 produced from MD cells can act as signals involved in MSC progenitor cell activation and migration contributing to development of JG hyperplasia.
Methods: The MMDD1 cell line was used as a model for MD cells. CD44+ MSCs were isolated by FACS from renal cortex of wild type C57BL/6 mice. Expression of PGE2 and PGI2 receptors was performed by microarray, RT-PCR, or western blot analysis. CD44+ cell migration was measured by transwell migration assay (BD Biosciences) or wound healing assay.
Results: Expression analysis revealed that CD44+ MSCs express the PGE2 receptors EP3 and EP4. Low levels of EP2 could also be detected. The PGI2 receptor was also expressed. Using the co-culture and scratch assay we found that co-culture of CD44+ MSCs with MMDD1 cells significantly increased CD44+ cells migration. These effects were abrogated in the presence of PGE2 receptor antagonists such as AH6809 and AH23848, but not by the IP antagonist CAY10441. Finally direct addition of PGE2 or PGI2 in CD44+ MSCs culture showed that PGE2, but not PGI2 increased CD44+ cells migration compared with vehicle treated cells.
Conclusion: Our results demonstrate that renal CD44+ MSCs express PGE2 receptors and these cells migrate in response to macula densa release of PGE2 suggesting a role for PGE2 in their activation during JG hyperplasia. In vivo experiments are currently in progress to address the physiological significance of this observation.
- © 2011 by American Heart Association, Inc.