TIPE2 deficiency accelerates neointima formation by downregulating smooth muscle cell differentiation

Zhang, Guizhong; Zhang, Wenqian; Lou, Yunwei; Xi, Wenjin; Cui, Jian; Geng, Minghong; Zhu, Faliang; Chen, Youhai H.; Liu, Suxia

doi:10.4161/cc.23325

Cited by 27 publications

(31 citation statements)

References 43 publications

(47 reference statements)

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“…74 TIPE2 may also be a negative inhibitor of atherosclerosis formation because TIPE2 inhibited smooth muscle proliferation and differentiation, whereas TIPE2 deficiency accelerated neointima formation. 75 In addition, TIPE2 regulates macrophage responses to oxidized low-density lipoproteins (ox-LDL); TIPE2-deficient macrophages produced more oxidative stress and inflammatory cytokines, with associated increases in JNK, NF-κB, and p38 signaling. 76 In conjunction with this finding, TIPE2 deficiency in the bone marrow increased atherosclerosis formation in Ldlr − / − mice fed a high-fat diet, and ox-LDL was found to downregulate TIPE2 mRNA expression.…”

Section: Tipe2 Is a Negative Regulator Of Immunity And Inflammationmentioning

confidence: 99%

Regulation of inflammation and tumorigenesis by the TIPE family of phospholipid transfer proteins

Goldsmith

Chen

2017

Cell Mol Immunol

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The TIPE (tumor necrosis factor-α-induced protein 8-like) family are newly described regulators of immunity and tumorigenesis consisting of four highly homologous mammalian proteins: TNFAIP8 (tumor necrosis factor-α-induced protein 8), TIPE1 (TNFAIP8-like 1, or TNFAIP8L1), TIPE2 (TNFAIP8L2) and TIPE3 (TNFAIP8L3). They are the only known transfer proteins of the lipid secondary messengers PIP2 (phosphatidylinositol 4,5-bisphosphate) and PIP3 (phosphatidylinositol 3,4,5-trisphosphate). Cell-surface receptors, such as G-protein-coupled receptors and receptor tyrosine kinases, regulate inflammation and cancer via several signaling pathways, including the nuclear factor (NF)-κB and phosphoinositide-3 kinase (PI3K) pathways, the latter of which is upstream of both Akt and STAT3 activation. An expression analysis in humans demonstrated that the TIPE family is dysregulated in cancer and inflammation, and studies both in mice and in vitro have demonstrated that this family of proteins plays a critical role in tumorigenesis and inflammatory responses. In this review, we summarize the current literature for all four family members, with a special focus on the phenotypic manifestations present in the various knockout murine strains, as well as the related cell signaling that has been elucidated to date.

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Section: Tipe2 Is a Negative Regulator Of Immunity And Inflammationmentioning

confidence: 99%

Regulation of inflammation and tumorigenesis by the TIPE family of phospholipid transfer proteins

Goldsmith

Chen

2017

Cell Mol Immunol

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“…In addition, the terpenoids of Rhizoma Alismatis have been reported to lower serum total cholesterol and LDL levels in ApoE-knockout atherosclerotic mice, induced by feeding with a high-fat diet [25]. In this study, VSMCs were cultured in vitro, and their transformation from a contractile to a synthetic phenotype was induced with Ox-LDL [26], so as to mimic the process of VSMC phenotypic transformation and migration in an in vivo model of atherosclerosis. Our findings showed that alisol A 24-acetate inhibited the phenotypic transformation and migration of VSMCs, which may be associated with the ERK1/2 signaling pathway.…”

Section: Discussionmentioning

confidence: 99%

Alisol A 24-Acetate, a Triterpenoid Derived from <b><i>Alisma orientale</i></b>, Inhibits Ox-LDL-Induced Phenotypic Transformation and Migration of Rat Vascular Smooth Muscle Cells through Suppressing ERK1/2 Signaling

Xue

Zhou²,

Wei³

et al. 2016

J Vasc Res

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Alisol A 24-acetate, a triterpenoid extracted from Alisma orientale, has shown antiatherosclerotic actions. The purpose of this study was to evaluate the inhibition of alisol A 24-acetate on oxidized low-density lipoprotein (Ox-LDL)-induced phenotypic transformation and migration of rat vascular smooth muscle cells (VSMCs), and to explore the underlying mechanisms. VSMCs were pretreated with alisol A 24-acetate and a specific extracellular signal-regulated kinase (ERK) inhibitor, U0126, and then stimulated with 50 mg/l Ox-LDL in vitro. The expression of VSMC phenotypic marker SM22α was determined using immunocytochemistry, and the migration of VSMCs was detected using a scratch-wound healing assay. The expression of matrix metalloproteinase (MMP)-9, MMP-2, phosphorylated ERK1/2 (pERK1/2) and total ERK was determined. Ox-LDL treatment caused a reduction in SM22α expression, VSMC transformation to the synthetic phenotype, increased MMP-2 and MMP-9 synthesis, the extension of VSMC migration distance and the upregulation of pERK1/2 expression, while the addition of alisol A 24-acetate or U0126 resulted in the elevation of SM22α expression, VSMC transformation to the contractile phenotype, a reduction in MMP-2 and MMP-9 expression, the shortening of cell migration distance and decreased pERK1/2 expression. The results of this study demonstrate that alisol A 24-acetateeffectively reverses the phenotypic transformation and inhibits the migration of VSMCs, which may be associated with the suppression of the ERK1/2 signaling pathway.

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“…Its deficiency in 129/J mice causes fatal inflammatory diseases [8] and abnormal expression in humans is associated with many kinds of diseases, such as hepatocellular carcinoma [7,10], stroke [11], HBV infection [12] and atherosclerosis [13,14]. Our previous studies showed that TIPE2 plays atheroprotective roles by negatively regulating ox-LDL-induced inflammatory responses in macrophages [13,14]. Furthermore, TIPE2 could inhibit neointima formation by regulating phenotypic switching of VSMCs during atherogenesis [13,14].…”

Section: Introductionmentioning

confidence: 95%

“…TNFAIP8L2 (TIPE2), the tumor necrosis factor (TNF)-α-induced protein 8 (TNFAIP8, TIPE) like 2, is a member of the TNFAIP8 family that plays important roles in controlling inflammation and tumorgenesis by suppressing RAS signaling [7][8][9][10]. Its deficiency in 129/J mice causes fatal inflammatory diseases [8] and abnormal expression in humans is associated with many kinds of diseases, such as hepatocellular carcinoma [7,10], stroke [11], HBV infection [12] and atherosclerosis [13,14]. Our previous studies showed that TIPE2 plays atheroprotective roles by negatively regulating ox-LDL-induced inflammatory responses in macrophages [13,14].…”

Section: Introductionmentioning

confidence: 99%

TIPE2 protein prevents injury-induced restenosis in mice

Zhang

Zhao

Wang

et al. 2015

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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Proliferation of vascular smooth muscle cells (VSMCs) plays an important role in restenosis, a disease characterized by smooth muscle cell hyperplasia and neointimal formation. How proliferation signals are controlled to avoid restenosis is not fully understood. Here we report that TIPE2, the tumor necrosis factor (TNF) α-induced protein 8-like 2 (TNFAIP8L2), suppresses injury-induced restenosis by inhibiting VSMCs proliferation. TIPE2 was significantly upregulated in VSMCs in response to PDGF-BB stimuli and injury. Enforced TIPE2 expression significantly suppressed VSMCs proliferation and cell cycle progression, whereas TIPE2 deficiency in VSMCs promoted cell proliferation and upregulated the expression of Cyclins D1 and D3. TIPE2 likely regulated VSMC proliferation via Rac1-STAT3 and ERK1/2 signaling pathways. It blocked STAT3 activation and nuclear translocation in a Rac1-dependent manner. As a result, TIPE2-deficient VSMCs exhibited enhanced proliferation whereas TIPE2-deficient mice developed more severe restenosis in response to vascular injury. Conversely, adenovirus-mediated gene transfer of TIPE2 significantly reduced injury-induced restenosis in mice. These results indicate that TIPE2 plays a suppressive role in injury-induced restenosis and may serve as a new therapeutic target for treating the disease.

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TIPE2 deficiency accelerates neointima formation by downregulating smooth muscle cell differentiation

Cited by 27 publications

References 43 publications

Regulation of inflammation and tumorigenesis by the TIPE family of phospholipid transfer proteins

Regulation of inflammation and tumorigenesis by the TIPE family of phospholipid transfer proteins

Alisol A 24-Acetate, a Triterpenoid Derived from <b><i>Alisma orientale</i></b>, Inhibits Ox-LDL-Induced Phenotypic Transformation and Migration of Rat Vascular Smooth Muscle Cells through Suppressing ERK1/2 Signaling

TIPE2 protein prevents injury-induced restenosis in mice

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