The grape-derived polyphenol resveratrol differentially affects epidermal and platelet-derived growth factor signaling in human liver myofibroblasts

Godichaud, S.; Si‐Tayeb, Karim; Augé, Nathalie; Desmoulière, Alexis; Balabaud, Charles; Payrastre, Bernard; Nègre‐Salvayre, Anne; Rosenbaum, Jean

doi:10.1016/j.biocel.2005.11.001

Cited by 26 publications

(27 citation statements)

References 29 publications

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“…Baicalin belongs to a class of polyphenols. Previous studies have shown that polyphenols inhibit PDGFRβ autophosphorylation [19][20][21][22]. Although the mechanisms underlying the inhibitory effect of these polyphenols remain to be established, previous studies suggested that some of these molecules may inhibit the activation of receptor tyrosine kinase by competing with adenosine triphosphate for binding to the kinase domain of the receptor, resulting in impaired activation of key signaling intermediates [23,24].…”

Section: Discussionmentioning

confidence: 99%

Baicalin inhibits PDGF-BB-stimulated vascular smooth muscle cell proliferation through suppressing PDGFRβ-ERK signaling and increase in p27 accumulation and prevents injury-induced neointimal hyperplasia

et al. 2010

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The increased proliferation and migration of vascular smooth muscle cells (VSMCs) are key events in the development of atherosclerotic lesions. Baicalin, an herb-derived flavonoid compound, has been previously shown to induce apoptosis and growth inhibition in cancer cells through multiple pathways. However, the potential role of baicalin in regulation of VSMC proliferation and prevention of cardiovascular diseases remains unexplored. In this study, we show that pretreatment with baicalin has a dose-dependent inhibitory effect on PDGF-BB-stimulated VSMC proliferation, accompanied with the reduction of proliferating cell nuclear antigen (PCNA) expression. We also show that baicalin-induced growth inhibition is associated with a decrease in cyclin E-CDK2 activation and increase in p27 level in PDGF-stimulated VSMCs, which appears to be at least partly mediated by blockade of PDGF receptor β (PDGFRβ)-extracellular signal-regulated kinase 1/2 (ERK1/2) signaling. In addition, baicalin was also found to inhibit adhesion molecule expression and cell migration induced by PDGF-BB in VSMCs. Furthermore, using an animal carotid arterial balloon-injury model, we found that baicalin significantly inhibited neointimal hyperplasia. Taken together, our results reveal a novel function of baicalin in inducing growth arrest of PDGF-stimulated VSMCs and suppressing neointimal hyperplasia after balloon injury, and suggest that the underlying mechanism involves the inhibition of cyclin E-CDK2 activation and the increase in p27 accumulation via blockade of the PDGFRβ-ERK1/2 signaling cascade.

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Section: Discussionmentioning

confidence: 99%

Baicalin inhibits PDGF-BB-stimulated vascular smooth muscle cell proliferation through suppressing PDGFRβ-ERK signaling and increase in p27 accumulation and prevents injury-induced neointimal hyperplasia

et al. 2010

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“…12,29 Activation of EGFR tyrosine kinase on ECM-producing cells has been essentially associated with the stimulation of cell proliferation. [10][11][12][13] We observed that AR treatment triggered signaling pathways such as ERK1/ 2, 38,39 FAK, 28 PI-3K/Akt, 25,28,39 and JNK 26 that are connected with cell proliferation in human and rodent liver fibrogenic cells. Consistently, through the EGFR/ ERK1/2 pathway, AR up-regulated the expression of growth-related transcription factors such as c-fos and Egr-1, and stimulated the growth and proliferation of mouse HSCs.…”

Section: Discussionmentioning

confidence: 94%

“…EGFR activation triggers intracellular pathways that may be relevant for the activation, proliferation, and survival of ECM-producing cells. 11,14,[25][26][27][28] We observed that incubation of LX-2 cells and mouse MFBs with AR rapidly induced the phosphorylation of the EGFR (Fig. 8A).…”

Section: Expression Of Fibrogenic Markers and Mediators In Ar؉/؉ And mentioning

confidence: 97%

The epidermal growth factor receptor ligand amphiregulin participates in the development of mouse liver fibrosis†

et al. 2008

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The hepatic wound-healing response to chronic noxious stimuli may lead to liver fibrosis, a condition characterized by excessive deposition of extracellular matrix. Fibrogenic cells, including hepatic stellate cells and myofibroblasts, are activated in response to a variety of cytokines, growth factors, and inflammatory mediators. The involvement of members of the epidermal growth factor family in this process has been suggested. Amphiregulin (AR) is an epidermal growth factor receptor (EGFR) ligand specifically induced upon liver injury. Here, we have addressed the in vivo role of AR in experimental liver fibrosis. To this end, liver fibrosis was induced in AR؉/؉ and AR؊/؊ mice by chronic CCl 4 administration. Histological and molecular markers of hepatic fibrogenesis were measured. Additionally, the response of cultured human and mouse liver fibrogenic cells to AR was evaluated. We observed that AR was expressed in isolated Kupffer cells and liver fibrogenic cells in response to inflamatory stimuli and platelet-derived growth factor, respectively. We demonstrate that the expression of ␣-smooth muscle actin and collagen deposition were markedly reduced in AR؊/؊ mice compared to AR؉/؉ animals. AR؊/؊ mice also showed reduced expression of tissue inhibitor of metalloproteinases-1 and connective tissue growth factor, two genes that responded to AR treatment in cultured fibrogenic cells. AR also stimulated cell proliferation and exerted a potent antiapoptotic effect on isolated fibrogenic cells. Conclusion: These results indicate that among the different EGFR ligands, AR plays a specific role in liver fibrosis. AR may contribute to the expression of fibrogenic mediators, as well as to the growth and survival of fibrogenic cells. Additionally, our data lend further support to the role of the EGFR system in hepatic fibrogenesis. ( Pio XII, n55, 31008 Pamplona, Spain. E-mail: maavila@unav.es (M.A.A.) and cberasain@unav.es (C.B.); fax: 34-948-194717.

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“…The absence of PTEN staining and the increase in p-AKT-positive cells in ACD lungs demonstrated that the PI3K/AKT pathway is activated and that loss of PTEN may be relevant to this activation. It has been reported that Foxf1 expression is directly inhibited by AKT in liver myofibroblasts (39). Therefore, it is possible that a similar situation occurs also in the lung where Foxf1 could be a direct transcriptional target for PTEN signaling in the lung mesenchyme through AKT activation.…”

Section: Mesodermal Pten Inactivation Disrupts Lung Vasculogenesismentioning

confidence: 92%

Mesodermal Pten inactivation leads to alveolar capillary dysplasia-like phenotype

Tiozzo

Carraro²,

Alam³

et al. 2012

J. Clin. Invest.

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Alveolar capillary dysplasia (ACD) is a congenital, lethal disorder of the pulmonary vasculature. Phosphatase and tensin homologue deleted from chromosome 10 (Pten) encodes a lipid phosphatase controlling key cellular functions, including stem/progenitor cell proliferation and differentiation; however, the role of PTEN in mesodermal lung cell lineage formation remains unexamined. To determine the role of mesodermal PTEN in the ontogeny of various mesenchymal cell lineages during lung development, we specifically deleted Pten in early embryonic lung mesenchyme in mice. Pups lacking Pten died at birth, with evidence of failure in blood oxygenation. Analysis at the cellular level showed defects in angioblast differentiation to endothelial cells and an accompanying accumulation of the angioblast cell population that was associated with disorganized capillary beds. We also found decreased expression of Forkhead box protein F1 (Foxf1), a gene associated with the ACD human phenotype. Analysis of human samples for ACD revealed a significant decrease in PTEN and increased activated protein kinase B (AKT). These studies demonstrate that mesodermal PTEN has a key role in controlling the amplification of angioblasts as well as their differentiation into endothelial cells, thereby directing the establishment of a functional gas exchange interface. Additionally, these mice could serve as a murine model of ACD.

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The grape-derived polyphenol resveratrol differentially affects epidermal and platelet-derived growth factor signaling in human liver myofibroblasts

Cited by 26 publications

References 29 publications

Baicalin inhibits PDGF-BB-stimulated vascular smooth muscle cell proliferation through suppressing PDGFRβ-ERK signaling and increase in p27 accumulation and prevents injury-induced neointimal hyperplasia

Baicalin inhibits PDGF-BB-stimulated vascular smooth muscle cell proliferation through suppressing PDGFRβ-ERK signaling and increase in p27 accumulation and prevents injury-induced neointimal hyperplasia

The epidermal growth factor receptor ligand amphiregulin participates in the development of mouse liver fibrosis†

Mesodermal Pten inactivation leads to alveolar capillary dysplasia-like phenotype

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