Adrenomedullin signaling is necessary for murine lymphatic vascular development
J. Clin. Invest. Kimberly L. Fritz-Six, et al. 118:40 doi:10.1172/JCI33302 [Go to this article.]

Figure 8
AM signaling preferentially mediates enhanced ERK activation in HMVEC-dLys compared with HUVECs. (A) Cultured HMVEC-dLys and HUVECs are morphologically and genetically distinct cell lines based on histology and expression pattern of Prox1. Original magnification, ×400. (B) Stimulation of HUVECs and HMVEC-dLys with the potent growth factor VEFGA resulted in a dose-dependant increase in cell proliferation that was not significantly different between the 2 cell lines. Data represent averages of 4 independent experiments, each performed in duplicate. (C) Stimulation of HUVECs and HMVEC-dLys with AM peptide resulted in a dose-dependant increase in cell proliferation that was significantly greater in HMVEC-dLys compared with HUVECs. *P < 0.05. Data represent averages of 4 independent experiments, each performed in duplicate. (D) Stimulation of HUVECs and HMVEC-dLys with 10 nM AM peptide resulted in a significantly greater induction of ERK phosphorylation in HMVEC-dLys compared with HUVECs over a 30-minute time course. *P < 0.03 at 15- and 20-minute time points. Data represent averages of 3 independent experiments, each performed in duplicate. (E) Induction of ERK activation by AM stimulation in HMVEC-dLys was significantly reduced by the RAMP2-specific peptide inhibitor AM_22-52 and completely blocked by the MAPK inhibitor PD98057 (PD). *P < 0.05 compared with untreated; ^#P < 0.05 compared with AM-treated. Data represent averages of 3 independent experiments, each performed in duplicate.