
DOI . ORG {
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Title[redir]:
Smad3 Specific Inhibitor, Naringenin, Decreases the Expression of Extracellular Matrix Induced by TGF-β1 in Cultured Rat Hepatic Stellate Cells | Pharmaceutical Research
Description:
Purpose During the process of liver fibrogenesis, transforming growth factor-β (TGF-β) plays an essential role in modulating extracellular matrix (ECM) gene expression, and a growing body of evidence suggests that this is a Smad3-dependent process in the activated hepatic stellate cells (HSCs). Naringenin showed a significantly protective effect on experimental rat liver fibrosis, in our efforts to elucidate its antifibrosis molecular mechanisms and to find a novel target based on Smad3 signaling for challenging fibrosis diseases. Methods In this study, reverse transcription-polymerase chain reaction and Western blot assays were used to investigate the inhibitory effect of naringenin on ECM formation induced by TGF-β1 in the HSC-T6 cells. Results Naringenin reduced not only the accumulation of ECM, including collagen Iα1 (Col Iα1), fibronectin (FN), and plasminogen activator inhibitor-1 (PAI-1), but also the production of Smad3 induced by TGF-β1 in both mRNA and protein levels in a dose-dependent manner. Moreover, naringenin selectively inhibited the transcription of Smad3, but not other Smads involved in TGF-β1 signaling pathways. Conclusion Our data demonstrate that naringenin can exert antifibrogenic effects by directly or indirectly down-regulating Smad3 protein expression and phosphorylation through TGF-β signaling.
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Keywords {🔍}
google, scholar, cas, article, pubmed, liver, smad, hepatic, cells, growth, fibrosis, naringenin, stellate, transforming, factor, activation, expression, tgfβ, beta, matrix, signaling, access, cell, research, extracellular, wang, fibrogenesis, tgfbeta, receptor, inhibition, privacy, cookies, content, inhibitor, wei, role, gene, plasminogen, activator, rats, biol, data, publish, search, induced, rat, liu, ecm, effect, collagen,
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month download article/chapter transforming growth factor-beta tgf-beta/smad gene targets phosphatidylinositol 3-kinase/akt-dependent suppression tgf-beta soluble receptor tgf-β1/smad/snon pathway transforming growth factor-β tgf-beta signaling pathways hepatic stellate cells related subjects tgf-β1 signaling pathways smad3/4-dependent transcriptional activation smad3 specific inhibitor extracellular matrix induced iglesias-de la cruz hepatic fibrosis proc tgf-β1/smad2/3 signaling full article pdf modulating extracellular matrix smad7 prevents activation plasminogen activator inhibitor-1 plasminogen activator inhibitor tgf-beta signaling mesangial cells biochem citrus flavonoid naringenin insulin involves activation hsc-t6 cells fat-storing cells privacy choices/manage cookies stellate cells noncollagenous matrix proteins inhibits transcriptional responses challenging fibrosis diseases type 1 receptor growth factor including collagen iα1 diabetic mouse kidney article liu transgenic mice results shenyang pharmaceutical university hepatic fibrosis tgf-β signaling check access instant access col iα1 %2bb2cnhvfw%3d 2186487 10 dose-dependent manner liver fibrosis liver fibrosis article log
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headline:Smad3 Specific Inhibitor, Naringenin, Decreases the Expression of Extracellular Matrix Induced by TGF-β1 in Cultured Rat Hepatic Stellate Cells
description:During the process of liver fibrogenesis, transforming growth factor-β (TGF-β) plays an essential role in modulating extracellular matrix (ECM) gene expression, and a growing body of evidence suggests that this is a Smad3-dependent process in the activated hepatic stellate cells (HSCs). Naringenin showed a significantly protective effect on experimental rat liver fibrosis, in our efforts to elucidate its antifibrosis molecular mechanisms and to find a novel target based on Smad3 signaling for challenging fibrosis diseases. In this study, reverse transcription-polymerase chain reaction and Western blot assays were used to investigate the inhibitory effect of naringenin on ECM formation induced by TGF-β1 in the HSC-T6 cells. Naringenin reduced not only the accumulation of ECM, including collagen Iα1 (Col Iα1), fibronectin (FN), and plasminogen activator inhibitor-1 (PAI-1), but also the production of Smad3 induced by TGF-β1 in both mRNA and protein levels in a dose-dependent manner. Moreover, naringenin selectively inhibited the transcription of Smad3, but not other Smads involved in TGF-β1 signaling pathways. Our data demonstrate that naringenin can exert antifibrogenic effects by directly or indirectly down-regulating Smad3 protein expression and phosphorylation through TGF-β signaling.
datePublished:2006-12-14T00:00:00Z
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headline:Smad3 Specific Inhibitor, Naringenin, Decreases the Expression of Extracellular Matrix Induced by TGF-β1 in Cultured Rat Hepatic Stellate Cells
description:During the process of liver fibrogenesis, transforming growth factor-β (TGF-β) plays an essential role in modulating extracellular matrix (ECM) gene expression, and a growing body of evidence suggests that this is a Smad3-dependent process in the activated hepatic stellate cells (HSCs). Naringenin showed a significantly protective effect on experimental rat liver fibrosis, in our efforts to elucidate its antifibrosis molecular mechanisms and to find a novel target based on Smad3 signaling for challenging fibrosis diseases. In this study, reverse transcription-polymerase chain reaction and Western blot assays were used to investigate the inhibitory effect of naringenin on ECM formation induced by TGF-β1 in the HSC-T6 cells. Naringenin reduced not only the accumulation of ECM, including collagen Iα1 (Col Iα1), fibronectin (FN), and plasminogen activator inhibitor-1 (PAI-1), but also the production of Smad3 induced by TGF-β1 in both mRNA and protein levels in a dose-dependent manner. Moreover, naringenin selectively inhibited the transcription of Smad3, but not other Smads involved in TGF-β1 signaling pathways. Our data demonstrate that naringenin can exert antifibrogenic effects by directly or indirectly down-regulating Smad3 protein expression and phosphorylation through TGF-β signaling.
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