title: Up-regulation of Rhoa/Rho kinase pathway by translationally controlled tumor protein in vascular smooth muscle cells.
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.
authors.affiliation: Graduate School of Pharmaceutical Sciences, College of Pharmacy, Ewha Womans University, Seoul 120-750, Korea. mengjeehye@hanmail.net.
authors.forename: Jeehye
authors.initials: J
authors.lastname: Maeng
authors.affiliation: Graduate School of Pharmaceutical Sciences, College of Pharmacy, Ewha Womans University, Seoul 120-750, Korea. vadimsheverdin@mail.ru.
authors.forename: Vadim
authors.initials: V
authors.lastname: Sheverdin
authors.affiliation: Graduate School of Pharmaceutical Sciences, College of Pharmacy, Ewha Womans University, Seoul 120-750, Korea. hk1028@hanmail.net.
authors.forename: Hyekyoung
authors.initials: H
authors.lastname: Shin
authors.affiliation: Graduate School of Pharmaceutical Sciences, College of Pharmacy, Ewha Womans University, Seoul 120-750, Korea. insu0623@gmail.com.
authors.forename: Insu
authors.initials: I
authors.lastname: Ha
authors.affiliation: Department of Pharmacology, Pusan National University-School of Medicine, Yangsan 626-870, Korea. sunsik@pusan.ac.kr.
authors.forename: Sun Sik
authors.initials: SS
authors.lastname: Bae
authors.affiliation: Institute of Molecular Biology, Academia Sinica, Taipei 11529, Taiwan. imbyy@gate.sinica.edu.tw.
authors.forename: Hsin-Fang
authors.initials: HF
authors.lastname: Yang-Yen
authors.affiliation: Graduate School of Pharmaceutical Sciences, College of Pharmacy, Ewha Womans University, Seoul 120-750, Korea. klyoon@ewha.ac.kr.
authors.forename: Kyunglim
authors.initials: K
authors.lastname: Lee
mesh_terms: D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000473:pathology; D014408:Biomarkers, Tumor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009131:Muscle, Smooth, Vascular / Q000166:cytology; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000378:metabolism*; D018994:Myosin Light Chains / Q000378:metabolism; D009219:Myosin-Light-Chain Kinase / Q000378:metabolism; D043263:Myosin-Light-Chain Phosphatase; D010766:Phosphorylation; D034622:RNA Interference; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D000090324:Tumor Protein, Translationally-Controlled 1; D015854:Up-Regulation; D054460:rho-Associated Kinases / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D018994:Myosin Light Chains; C000715647:TPT1 protein, human; C000715648:Tpt1 protein, mouse; C000715649:Tpt1 protein, rat; D000090324:Tumor Protein, Translationally-Controlled 1; D054460:rho-Associated Kinases; D009219:Myosin-Light-Chain Kinase; D043263:Myosin-Light-Chain Phosphatase; C510645:Ppp1r12a protein, mouse; D020742:rhoA GTP-Binding Protein