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The regulation of lymphangiogenic signaling in the epicardium
Author(s) -
Karunamuni Ganga,
Gu Shi,
Doughman Yong Qiu,
Bader David,
Scacheri Peter,
Watanabe Michiko
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.177.2
Subject(s) - embryonic stem cell , mapk/erk pathway , microbiology and biotechnology , lymphatic system , vascular endothelial growth factor , vascular endothelial growth factor c , lymphangiogenesis , biology , chemistry , cancer research , signal transduction , endocrinology , medicine , vascular endothelial growth factor a , immunology , vegf receptors , cancer , biochemistry , metastasis , gene
We have demonstrated that the cardiac lymphatics are derived in part from mesothelial cells in the embryonic epicardium, and that their development is impacted by VEGFR‐3 inhibition. In this study, we explored the mechanisms that may affect lymphatic differentiation in pluripotent epicardial cells. Adult and embryonic epicardial cells were treated with the lymphangiogenic growth factor VEGF‐C, resulting in a dramatic increase in nuclear expression for Prox‐1, a master lymphatic regulatory gene, within 5 min of VEGF‐C administration. The nuclear accumulation of Prox‐1 was not observed after FGF or VEGF‐A treatment. The ERK inhibitor UO126 induced a decrease in Prox‐1 expression in nuclei in both untreated and VEGF‐C treated cells, suggesting that activated ERK may regulate Prox‐1 nuclear accumulation. Inhibiting ERK function in the epicardium also inhibited cell migration and differentiation. Our studies suggest that the lymphangiogenic growth factor VEGF‐C binds to VEGFR‐3 and acts via ERK to stimulate nuclear accumulation of Prox‐1, in adult and embryonic epicardial cells. Preliminary findings suggest that tissue oxygen levels, mediated by the hypoxia inducible factor HIF‐1, may also regulate lymphangiogenic signaling in the epicardium. Source of Research Support: R01 HL091171(ARRA), ES013507, AHA 0715153B. Grant Funding Source: NIH