Up-regulation of RhoA/Rho kinase pathway by translationally controlled tumor protein in vascular smooth muscle cells

Jeehye Maeng, Vadim Sheverdin, Hyekyoung Shin, Insu Ha, Sun Sik Bae, Hsin Fang Yang-Yen, Kyunglim Lee

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

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 OPEN ACCESS plays a role in the regulation in vasculature. Modulation of TCTP may offer a therapeutic target for hypertension and in vascular contractility dysfunction.

Original languageEnglish
Pages (from-to)10365-10376
Number of pages12
JournalInternational Journal of Molecular Sciences
Volume15
Issue number6
DOIs
StatePublished - 10 Jun 2014

Keywords

  • Contraction
  • Hypertension
  • Myosin light chain (MLC)
  • RhoA
  • Translationally controlled tumor protein (TCTP)
  • Vascular smooth muscle cell (VSMC)

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