E-Cadherin/β-Catenin/T-Cell Factor Pathway Is Involved in Smooth Muscle Cell Proliferation Elicited by Oxidized Low-Density Lipoprotein

Bedel, Aurélie; Nègre‐Salvayre, Anne; Heeneman, Sylvia; Grazide, Marie-Hélène; Thiers, Jean-Claude; Salvayre, Robert; Maupas-Schwalm, Françoise

doi:10.1161/circresaha.107.166405

Cited by 56 publications

(54 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This signaling has critical roles in the regulation of VSMC proliferation and migration and in vascular remodeling. [16][17][18][19] We found that the β-catenin signaling pathway was activated under Ang II stimulation. Overexpression of exogenous Nur77 in VSMCs or 293T cells downregulated the expression of β-catenin, accompanied by reduction in the transcriptional activity of β-catenin, and the expression of its target gene that controls VSMC proliferation.…”

Section: Discussionmentioning

confidence: 87%

“…[16][17][18][19] Therefore, we first investigated whether β-catenin signaling was activated in Ang II-induced vascular remodeling. Ang II significantly induced the upregulation of active β-catenin (reaching a plateau at 30 to 60 minutes; Figure 5A).…”

Section: Ang II Activates the β-Catenin Signaling Pathway Which Is Amentioning

confidence: 99%

“…14,15 Many studies have revealed the critical pathophysiological roles of the Wnt/β-catenin pathway in vascular remodeling. [16][17][18][19] Tsaousi et al 18 found that Wnt4/β-catenin signaling induces VSMC proliferation and is associated with intimal thickening in ligated arteries. Diverse physiological stimuli, including oxidized low-density lipoprotein and growth factors, activate β-catenin signaling in VSMCs.…”

mentioning

confidence: 99%

“…Diverse physiological stimuli, including oxidized low-density lipoprotein and growth factors, activate β-catenin signaling in VSMCs. 18,19 Activation of Wnt signaling results in the accumulation of cytosolic nonphosphorylated β-catenin (stable and active forms), and its subsequent translocation to the nucleus to induce the transcription of multiple target genes (eg, cyclin D1, c-myc, matrix metalloproteinases [MMPs]), which promote VSMC proliferation and migration. The interplay between Nur77 and the Wnt/β-catenin signaling pathway in cancer cells has been well reported in in vitro and in vivo settings.…”

mentioning

confidence: 99%

See 3 more Smart Citations

Orphan Nuclear Receptor Nur77 Inhibits Angiotensin II–Induced Vascular Remodeling via Downregulation of β-Catenin

et al. 2016

View full text Add to dashboard Cite

Angiotensin II (Ang II) is the predominant effector peptide of the renin–angiotensin system. Ang II contributes to vascular remodeling in many cardiovascular diseases (eg, hypertension, atherosclerosis, restenosis, and aneurysm). Orphan nuclear receptor Nur77 has a crucial role in the functional regulation of vascular cells. The objective of this study was to define the specific role of Nur77 in Ang II–induced vascular remodeling. Nur77 expression was initially found to be elevated in medial vascular smooth muscle cells (VSMCs) of thoracic aortas from mice continuously infused with Ang II for 2 weeks using a subcutaneous osmotic minipump. Cellular studies revealed that Nur77 expression was upregulated by Ang II via the MAPK/PKA-CREB signaling pathway. Ang II–induced proliferation, migration, and phenotypic switching were significantly enhanced in VSMCs isolated from Nur77 −/− mice compared with wild-type VSMCs. Consistent with the role in VSMCs, we found that compared with wild-type mice, Nur77 −/− mice had elevated aortic medial areas and luminal diameters, more severe elastin disruption and collagen deposition, increased VSMC proliferation and matrix metalloproteinase production, and decreased VSMC-specific genes SM-22α and α-actin expression, after 2 weeks of exogenous Ang II administration. The results of additional experiments suggested that Nur77 suppressed Ang II–induced β-catenin signaling pathway activation by promoting β-catenin degradation and inhibiting its transcriptional activity. Our findings indicated that Nur77 is a critical negative regulator of Ang II–induced VSMC proliferation, migration, and phenotypic switching via the downregulation of β-catenin activity. Nur77 may reduce Ang II–induced vascular remodeling involved in many cardiovascular diseases.

show abstract

Section: Discussionmentioning

confidence: 87%

Section: Ang II Activates the β-Catenin Signaling Pathway Which Is Amentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Orphan Nuclear Receptor Nur77 Inhibits Angiotensin II–Induced Vascular Remodeling via Downregulation of β-Catenin

et al. 2016

View full text Add to dashboard Cite

show abstract

“…7,10,43 Oxidized LDL has also been shown to stimulate smooth muscle cell migration in a mechanism that was dependent on b-catenin signaling. 44 A number of confirmed Wnt target genes, including versican, 19 fibronectin 45 and matrix metalloproteases, 46 are upregulated after vascular injury and appear to promote inflammation and atheroma formation. [47][48][49] Our data add to this story by suggesting canonical Wnt signaling promotes a contractile and secretory phenotype in vascular smooth muscle cells.…”

Section: Discussionmentioning

confidence: 99%

WNT3A induces a contractile and secretory phenotype in cultured vascular smooth muscle cells that is associated with increased gap junction communication

Carthy

Luo

McManus

2012

Laboratory Investigation

View full text Add to dashboard Cite

Evidence suggests a role for Wnt signaling in vascular wound repair and remodeling events. Despite this, very little is known about the effect of Wnt ligands on the structure and function of vascular cells. In this study, we treated vascular smooth muscle cells with 250 ng/ml of recombinant Wnt3a for 72 h and observed changes in the cell phenotype. Our data suggest Wnt3a completely alters the phenotype of vascular smooth muscle cells. The Wnt3a-treated cells appeared larger and had increased formation of stress fibers. These cells also had increased expression of the smooth muscle contractile proteins, calponin and smooth muscle a-actin, and contracted a collagen lattice faster than control cells. The Wnt3a-treated smooth muscle cells displayed increased extracellular matrix synthesis, as measured by collagen I and III mRNA expression, along with increased expression of MMP2 and MMP9, but decreased TIMP2 levels. The Wnt3a-induced change in cell phenotype was associated with increased expression of the gap junction protein connexin 43. Consistent with this, Wnt3a-treated smooth muscle cells displayed enhanced intercellular communication, as measured by the scrape-loading dye transfer technique. The canonical Wnt antagonist, dickkopf-related protein 1, completely reversed the contractile protein and connexin 43 expression seen in the Wnt3a-treated cells, suggesting these changes were dependent on canonical Wnt signaling. Collectively, this data suggest Wnt3a promotes a contractile and secretory phenotype in vascular smooth muscle cells that is associated with increased gap junction communication. Numerous studies have demonstrated that after arterial injury, vessel walls follow a response-to-injury pattern of wound healing leading to stenosis secondary to the neointimal accumulation of smooth muscle cells and extracellular matrix. 1-4 A number of soluble mediators released at the site of vascular injury act as molecular cues that guide smooth muscle cell responses during repair. 5,6 Growing evidence suggest a role for the Wnt family of secreted glycoproteins and their associated signaling pathways in regulating many of the processes involved in vascular wound repair and remodeling events. [7][8][9][10][11][12][13][14] However, the precise mechanisms and outcomes of Wnt signaling in such settings remain unclear. Moreover, the effect of specific Wnt family members on vascular cell phenotype remain undefined.The Wnt signaling pathway is best recognized for its role in the development of multi-cellular organisms, 15,16 and is critically involved in normal heart formation. 17 The Wnt family is comprised of 19 secreted glycoproteins that bind the Frizzled receptor and its co-receptor, lipoprotein receptorrelated proteins 5/6, to initiate an intracellular signaling cascade that controls the turnover of b-catenin. 18 In the absence of Wnt ligand, b-catenin is targeted for ubiquitinmediated degradation by the 26S proteasome. However, upon ligand stimulation, canonical Wnt signaling triggers a series of phosphorylation even...

show abstract

miR-1290 promotes IL-8-mediated vascular endothelial cell adhesion by targeting GSK-3β

Cui

Liu

et al. 2021

Mol Biol Rep

View full text Add to dashboard Cite

E-Cadherin/β-Catenin/T-Cell Factor Pathway Is Involved in Smooth Muscle Cell Proliferation Elicited by Oxidized Low-Density Lipoprotein

Cited by 56 publications

References 49 publications

Orphan Nuclear Receptor Nur77 Inhibits Angiotensin II–Induced Vascular Remodeling via Downregulation of β-Catenin

Orphan Nuclear Receptor Nur77 Inhibits Angiotensin II–Induced Vascular Remodeling via Downregulation of β-Catenin

WNT3A induces a contractile and secretory phenotype in cultured vascular smooth muscle cells that is associated with increased gap junction communication

miR-1290 promotes IL-8-mediated vascular endothelial cell adhesion by targeting GSK-3β

Contact Info

Product

Resources

About