Chronic activation of the prostaglandin receptor EP4 promotes hyaluronan-mediated neointimal formation in the ductus arteriosus
J. Clin. Invest. Utako Yokoyama, et al. 116:3026 doi:10.1172/JCI28639 [Go to this article.]

Figure 2
Effects of chronic EP4 stimulation on DA SMC migration. (A) Cell migration and HA production in response to long exposures (>24 hours) to ONO-AE1-329 (10^–6 M). SMC migration (bar graph) and HA secretion into the media (line graph) are shown. An increase in HA production in culture media was accompanied by the time-dependent increase in SMC migration. n = 4–8; **P < 0.01, ^#P < 0.001 compared with control. ^†P < 0.05, ^ΧP < 0.001 compared with HA production at 24 hours. (B) ONO-AE1-329–induced HA production is responsible for increased migration. The ONO-AE1-329–induced SMC migration was significantly attenuated by daily exchange of culture media (EXC); addition of hyaluronidase (HAD) (0.02 mg/ml: HAD 0.02; 0.05 mg/ml: HAD 0.05) to culture media; or transfection with rat HAS2 siRNA (100 pmol). HA (50 ng/ml: HA 50; 200 ng/ml: HA 200) alone was sufficient to stimulate DA SMC migration to the same or a higher level as was ONO-AE1-329 (10^–6 M). n = 4; **P < 0.01, ^#P < 0.001 compared with control (10^–6 M ONO-AE1-329).