| First Author | Arboleda-Velasquez JF | Year | 2014 |
| Journal | Invest Ophthalmol Vis Sci | Volume | 55 |
| Issue | 8 | Pages | 5191-9 |
| PubMed ID | 25015359 | Mgi Jnum | J:230134 |
| Mgi Id | MGI:5755552 | Doi | 10.1167/iovs.14-14046 |
| Citation | Arboleda-Velasquez JF, et al. (2014) Notch signaling functions in retinal pericyte survival. Invest Ophthalmol Vis Sci 55(8):5191-9 |
| abstractText | PURPOSE: Pericytes, the vascular cells that constitute the outer layer of capillaries, have been shown to have a crucial role in vascular development and stability. Loss of pericytes precedes endothelial cell dysfunction and vascular degeneration in small-vessel diseases, including diabetic retinopathy. Despite their clinical relevance, the cellular pathways controlling survival of retinal pericytes remain largely uncharacterized. Therefore, we investigated the role of Notch signaling, a master regulator of cell fate decisions, in retinal pericyte survival. METHODS: A coculture system of ligand-dependent Notch signaling was developed using primary cultured retinal pericytes and a mesenchymal cell line derived from an inducible mouse model expressing the Delta-like 1 Notch ligand. This model was used to examine the effect of Notch activity on pericyte survival using quantitative PCR (qPCR) and a light-induced cell death assay. The effect of Notch gain- and loss-of-function was analyzed in monocultures of retinal pericytes using antibody arrays to interrogate the expression of apoptosis-related proteins. RESULTS: Primary cultured retinal pericytes differentially expressed key molecules of the Notch pathway and displayed strong expression of canonical Notch/RBPJK (recombination signal-binding protein 1 for J-kappa) downstream targets. A gene expression screen using gain- and loss-of-function approaches identified genes relevant to cell survival as downstream targets of Notch activity in retinal pericytes. Ligand-mediated Notch activity protected retinal pericytes from light-induced cell death. CONCLUSIONS: Our results have identified signature genes downstream of Notch activity in retinal pericytes and suggest that tight regulation of Notch signaling is crucial for pericyte survival. |
