| First Author | Nurminskaya M | Year | 2014 |
| Journal | J Vasc Res | Volume | 51 |
| Issue | 6 | Pages | 418-28 |
| PubMed ID | 25612735 | Mgi Jnum | J:318304 |
| Mgi Id | MGI:6859134 | Doi | 10.1159/000369461 |
| Citation | Nurminskaya M, et al. (2014) Transglutaminase 2 promotes PDGF-mediated activation of PDGFR/Akt1 and beta-catenin signaling in vascular smooth muscle cells and supports neointima formation. J Vasc Res 51(6):418-28 |
| abstractText | BACKGROUND: Phenotypic switch of vascular smooth muscle cells (VSMCs) accompanies neointima formation and associates with vascular diseases. Platelet-derived growth factor (PDGF)-induced activation of PDGFR/Akt1 and beta-catenin signaling pathways in VSMCs has been implicated in vessel occlusion. Transglutaminase 2 (TG2) regulates these pathways and its levels are increased in the neointima. OBJECTIVE: The aim of this study was to evaluate the role of TG2 in PDGF/beta-catenin signaling cross-talk and assess its contribution to neointima. METHODS: Aortic VSMCs from wild-type and TG2 knockout mice were tested in vitro for levels of VSMC markers, proliferation, migration and PDGF-induced activation of PDGFR/Akt1 and beta-catenin pathways. Neointima in these mice was studied ex vivo in coronary vessels using a heart slice model and in vivo using a carotid artery ligation model. RESULTS: Genetic deletion of TG2 attenuated the PDGF-induced phenotypic switch of aortic VSMCs, reduced their proliferation and migration rates, and inhibited PDGF-induced activation of PDGFR/Akt1 and beta-catenin pathways in both ex vivo and in vivo neointima models. Importantly, genetic deletion of TG2 also markedly attenuated vessel occlusion. CONCLUSIONS: TG2 promotes neointima formation by mediating the PDGF-induced activation of the PDGFR/Akt1 and beta-catenin pathways in VSMCs. This study identifies TG2 as a potential therapeutic target for blocking neointima in blood vessels. |
