Abstract: Translationally controlled tumor protein (TCTP), a repressor for Na,K-ATPase has been implicated in the development of systemic hypertension, as proved by TCTP-over-expressing transgenic (TCTP-TG) mice. Aorta of TCTP-TG exhibited hypercontractile response compared to that of non-transgenic mice (NTG) suggesting dys-regulation of signaling pathways involved in the vascular contractility by TCTP. Because dys-regulation of RhoA/Rho kinase pathway is implicated in increased vascular contractility, we examined whether TCTP induces alterations in RhoA pathway in vascular smooth muscle cells (VSMCs). We found that TCTP over-expression by adenovirus infection up-regulated RhoA pathway including the expression of RhoA, and its downstream signalings, phosphorylation of myosin phosphatase target protein (MYPT-1), and myosin light chain (MLC). Conversely, lentiviral silencing of TCTP reduced the RhoA expression and Rho kinase signalings. Using immunohistochemical and Western blotting studies on aortas from TCTP-TG confirmed the elevated expression of RhoA and increase in p-MLC (phosphorylated MLC). In contrast, down-regulation of RhoA and p-MLC were found in aortas from heterozygous mice with deleted allele of TCTP (TCTP+/−). We conclude that up-regulation of TCTP induces RhoA-mediated pathway, and that TCTP-induced RhoA plays a role in the regulation in vasculature. Modulation of TCTP may offer a therapeutic target for hypertension and in vascular contractility dysfunction.
Keywords: contraction; hypertension; myosin light chain (MLC); RhoA; translationally controlled tumor protein (TCTP); vascular smooth muscle cell (VSMC)
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Maeng, J.; Sheverdin, V.; Shin, H.; Ha, I.; Bae, S.S.; Yang-Yen, H.-F.; Lee, K. Up-Regulation of Rhoa/Rho Kinase Pathway by Translationally Controlled Tumor Protein in Vascular Smooth Muscle Cells. Int. J. Mol. Sci. 2014, 15, 10365-10376.
Maeng J, Sheverdin V, Shin H, Ha I, Bae SS, Yang-Yen H-F, Lee K. Up-Regulation of Rhoa/Rho Kinase Pathway by Translationally Controlled Tumor Protein in Vascular Smooth Muscle Cells. International Journal of Molecular Sciences. 2014; 15(6):10365-10376.
Maeng, Jeehye; Sheverdin, Vadim; Shin, Hyekyoung; Ha, Insu; Bae, Sun S.; Yang-Yen, Hsin-Fang; Lee, Kyunglim. 2014. "Up-Regulation of Rhoa/Rho Kinase Pathway by Translationally Controlled Tumor Protein in Vascular Smooth Muscle Cells." Int. J. Mol. Sci. 15, no. 6: 10365-10376.