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Fig. 5 (A) Tetracycline-regulated expression of BirA-MEKK3 drives dose-dependent expression of KLF2 and KLF4 in HUVEC. (B) siRNA knockdown of MEKK3 in HUVEC blocks flow-induced expression of KLF2, KLF4 and ADAMTS4. HUVEC were exposed to 16 hr of laminar shear after exposure to siRNA directed against MEKK3 (MAP3K3) or control, scrambled siRNA. N = 5; p < 0.0001. (C) qPCR of E10.5 hearts reveals severely reduced levels of Klf2, Klf4 and known KLF2/4 target genes following endocardial Mekk3 (Map3k3) deletion. N = 3 for all groups. (D) qPCR of E10.5 hearts reveals reduced levels of Nrg1 and Adamts5 but normal levels of FGFs following endocardial Mekk3 (Map3k3) deletion. N = 3 for all groups. (E) qPCR of E9.5 wild-type mouse hearts following 24 hr incubation in medium containing the MEK5 inhibitor BIX02188 (“BIX”) or DMSO (“control”). N = 3 for all groups. Error bars represent SEM. ∗p < 0.05; ∗∗p < 0.01; ∗∗∗p < 0.001; ∗∗∗∗p < 0.0001.
Reprinted from Developmental Cell, 32, Zhou, Z., Rawnsley, D.R., Goddard, L.M., Pan, W., Cao, X.J., Jakus, Z., Zheng, H., Yang, J., Arthur, J.S., Whitehead, K.J., Li, D., Zhou, B., Garcia, B.A., Zheng, X., Kahn, M.L., The cerebral cavernous malformation pathway controls cardiac development via regulation of endocardial MEKK3 signaling and KLF expression, 168-80, Copyright (2015) with permission from Elsevier. Full text @ Dev. Cell