Int. J. Mol. Sci. 2014, 15(6), 10365-10376; doi:10.3390/ijms150610365
Article

Up-Regulation of Rhoa/Rho Kinase Pathway by Translationally Controlled Tumor Protein in Vascular Smooth Muscle Cells

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Received: 25 April 2014; in revised form: 30 May 2014 / Accepted: 3 June 2014 / Published: 10 June 2014
(This article belongs to the Section Molecular Pathology)
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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)
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

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.

AMA Style

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.

Chicago/Turabian Style

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.


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