title: TIPE2 deficiency accelerates neointima formation by downregulating smooth muscle cell differentiation.
abstract: Phenotypic switching of vascular smooth muscle cells (VSMCs) is known to play a key role in the development of atherosclerosis. However, the mechanisms that mediate VSMC phenotypic switching are unclear. We report here that TIPE2, the tumor necrosis factor (TNF) α-induced protein 8-like 2 (TNFAIP8L2), plays an atheroprotective role by regulating phenotypic switching of VSMCs in response to oxidized low-density lipoprotein (ox-LDL) stimuli. TIPE2-deficient VSMCs treated with ox-LDL expressed lower levels of contractile proteins such as SMαA, SM-MHC and calponin, whereas the proliferation, migration and the synthetic capacity for growth factors and cytokines were increased remarkably. Furthermore, TIPE2 inhibited VSMCs proliferation by preventing G 1/S phase transition. Interestingly, these effects of TIPE2 on VSMCs were dependent on P38 and ERK1/2 kinase signals. As a result, neointima formation was accelerated in the carotid arteries of TIPE2-deficient mice. These results indicate that TIPE2 is a potential inhibitor of atherosclerosis.
authors: Institute of Immunology, Shandong University School of Medicine, Ji'nan, China.
authors: Guizhong
authors: G
authors: Zhang
authors: Wenqian
authors: W
authors: Zhang
authors: Yunwei
authors: Y
authors: Lou
authors: Wenjin
authors: W
authors: Xi
authors: Jian
authors: J
authors: Cui
authors: Minghong
authors: M
authors: Geng
authors: Faliang
authors: F
authors: Zhu
authors: Youhai H
authors: YH
authors: Chen
authors: Suxia
authors: S
authors: Liu
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000096:biosynthesis; D002339:Carotid Arteries / Q000473:pathology; D002454:Cell Differentiation; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D003285:Contractile Proteins / Q000096:biosynthesis; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D059585:G1 Phase Cell Cycle Checkpoints; D047908:Intracellular Signaling Peptides and Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D020935:MAP Kinase Signaling System; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008840:Microfilament Proteins / Q000096:biosynthesis; D009131:Muscle, Smooth, Vascular / Q000166:cytology; D032389:Myocytes, Smooth Muscle / Q000502:physiology*; D058426:Neointima / Q000473:pathology*; D010641:Phenotype; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism; D000096985:Calponins
chemical_list: D002135:Calcium-Binding Proteins; D003285:Contractile Proteins; D048049:Extracellular Signal-Regulated MAP Kinases; D047908:Intracellular Signaling Peptides and Proteins; D008077:Lipoproteins, LDL; D008840:Microfilament Proteins; D048051:p38 Mitogen-Activated Protein Kinases; D000096985:Calponins; C529002:TIPE2 protein, mouse; C099252:oxidized low density lipoprotein
keywords: TNFAIP8L2 (TIPE2); atherosclerosis; cell cycle; phenotypic switching; vascular smooth muscle cell