Involvement of C/EBP-α gene in in vitro activation of rat hepatic stellate cells

Huang, Guangjian; Zhang, Jin Sheng; Tang, Qi

doi:10.1016/j.bbrc.2004.09.196

Cited by 32 publications

(38 citation statements)

References 70 publications

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“…Park et al (2011) reported that the HFD-fed mice were characterized by increases in gene expressions of the hepatic fibrosis markers such as a-SMA and collagen. Numerous studies have demonstrated that adipocyte differentiation and oxidative stress induced hepatic fibrosis and development of NAFLD (Huang et al 2004;Kim et al 2012;Lee et al 2001). The current study could give a clue for a beneficial effect of MLE supplementation on hepatic fibrosis by decreases in a-SMA and collagen gene expression as well as a-SMA protein in the HFD-induced NAFLD.…”

Section: Discussionmentioning

confidence: 54%

“…In response to oxidative stress, hepatic stellate cells (HSCs) transform into proliferative, fibrogenic, proinflammatory, and contractile myofibroblasts, which express a-smooth muscle actin (a-SMA) and type 1 collagen (Huang et al 2004;Lee et al 2001). Park et al (2011) reported that the HFD-fed mice were characterized by increases in gene expressions of the hepatic fibrosis markers such as a-SMA and collagen.…”

Section: Discussionmentioning

confidence: 99%

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Mulberry leaves (Morus alba L.) ameliorate obesity-induced hepatic lipogenesis, fibrosis, and oxidative stress in high-fat diet-fed mice

2015

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Obesity is associated with chronic diseases such as fatty liver, type 2 diabetes, cardiovascular disease, and severe metabolic syndrome. Obesity causes metabolic impairment including excessive lipid accumulation and fibrosis in the hepatic tissue as well as the increase in oxidative stress. In order to investigate the effect of mulberry leaf (Morus alba L.) extract (MLE) on obesity-induced oxidative stress, lipogenesis, and fibrosis in liver, MLE has been gavaged for 12 weeks in high-fat diet (HFD)-induced obese mice. MLE treatment significantly ameliorated LXRa-mediated lipogenesis and hepatic fibrosis markers such as a-smooth muscle actin, while MLE up-regulated lipolysis-associated markers such as lipoprotein lipase in the HFD-fed mice. Moreover, MLE normalized the activities of antioxidant enzymes including heme oxygenase-1 and glutathione peroxidase in accordance with protein levels of 4-hydroxynonenal in the HFDfed mice. MLE has beneficial effects on obesity-related fatty liver disease by regulation of hepatic lipid metabolism, fibrosis, and antioxidant defense system. MLE supplementation might be a potential therapeutic approach for obesity-related disease including non-alcoholic fatty liver disease.

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Section: Discussionmentioning

confidence: 54%

Section: Discussionmentioning

confidence: 99%

Mulberry leaves (Morus alba L.) ameliorate obesity-induced hepatic lipogenesis, fibrosis, and oxidative stress in high-fat diet-fed mice

2015

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“…HSC-T6 cells, an immortalized rat hepatic stellate cell line, have been widely used as an in vitro assay system to study the action mechanism of the anti-fibrotic agents. It is particularly valuable for studies of retinoid metabolism based on their similar retinoid phenotype as primary cells [23].Our previous research also found that over-expression of C/EBP-a could induce apoptosis of primary cultured rat HSCs and rat HSC cell line HSC-T6 simultaneously [18], so we chose HSC-T6 as a representative for HSCs. In addition, we chose BRL-3A, a rat hepatocyte cell line, as a representative for hepatocytes, which was proved to be feasible in our previous research [24].…”

Section: Discussionmentioning

confidence: 98%

“…C/EBP-a alone induces preadipocyte maturation and regulates the expression of adipogenic genes. Importantly, C/EBP-a negatively regulates the cell cycle of adipocytes and other cell types through its interaction with p21Cip1/WAF1, E2F, or cyclin-dependent kinase type 2 or type 4 (CDK2 or CDK4) and retinoblastoma protein (pRB) [14][15][16][17][18].…”

Section: Introductionmentioning

confidence: 99%

C/EBP-α ameliorates CCl4-induced liver fibrosis in mice through promoting apoptosis of hepatic stellate cells with little apoptotic effect on hepatocytes in vitro and in vivo

et al. 2012

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CCAAT enhancer binding protein-α (C/EBP-α) is a transcript factor that regulates adipocyte differentiation and induces apoptosis in hepatic stellate cells (HSCs) in vivo and in vitro. However, the effect of C/EBP-α on hepatocytes in vivo remains unknown. This study investigated whether C/EBP-α exerts different apoptotic effects on hepatocytes and HSCs in vitro and in vivo. An adenovirus vector-expressing C/EBP-α gene was constructed, and a rat hepatic stellate cell lines (HSC-T6) and hepatocytes were transfected. A CCl(4)-induced liver fibrosis model in mice was also utilized. C/EBP-α induced apoptosis in hepatocytes and HSCs, but a significant difference between these cell types was observed in vitro. The mitochondrial pathway was involved in the apoptotic process and was predominant in HSC-T6 apoptosis. In the CCl(4)-induced mice liver fibrosis model, the administration of Ad-C/EBP-α decreased extracellular matrix deposition, including collagen and hydroxyproline content, and γ-GT levels, a marker of liver damage, were reduced significantly. Immunohistochemistry and TUNEL assay results showed an increase of apoptosis in HSCs, but hepatocytes were less affected. C/EBP-α induced differential apoptotic effects in hepatocytes and HSCs in vitro and in vivo. This differential effect could be a potential target for the treatment of hepatic fibrosis with little hepatic toxicity.

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“…Huang et al [37] demonstrated that hepatic fibrosis and development of NAFLD are induced by differentiation of adipocyte and oxidative stress. The current study could give a clue for the first time on the beneficial effect of MA and MR extracts supplementation on cardiac dysfunction and fibrosis by attenuating ROS, vascular function, lipid accumulation, inflammation, and reduced collagen in the HFDinduced obesity.…”

Section: Discussionmentioning

confidence: 99%

Therapeutic Impact of Berries (Morus Alba and Morus Rubra) Fruit Extract in the Regression of High-Fat Diet-Induced Cardiac Dysfunction in Rats

Baz

Aly

Abd‐Alla

et al. 2018

Asian J Pharm Clin Res

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Objective: The aim of the present study is to investigate the effect of Morus alba (MA) and Morus rubra L. (MR) fruit extract on obesity-induced cardiac dysfunction and fibrosis in cardiac tissue.Methods: Seventy male Wistar albino rats were randomly divided into five groups of ten rats each. MA and MR have been administered for 6 weeks in obese rats induced by high-fat diet (HFD). Adiponectin, glucagon, troponin, plasminogen activator inhibitor, cell adhesion molecules-1 (intracellular and vascular respectively), C-reactive protein, collagen type II and collagen alpha-1 (III) chain, and lipoxygenase activity were also estimated in serum of obese rats. Histopathological investigation of cardiac tissue was carried out.Results: MA and MR treatments significantly normalized cardiac dysfunction biomarkers as well as cardiac fibrosis as examined by histopathological examination with higher percentage of improvement for MR extract. Conclusion:Hence, it could be concluded that MA and MR extracts have useful effects on obesity-associated cardiac diseases through lipid metabolism regulation, cardiac functions and reversed cardiac fibrosis.

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Involvement of C/EBP-α gene in in vitro activation of rat hepatic stellate cells

Cited by 32 publications

References 70 publications

Mulberry leaves (Morus alba L.) ameliorate obesity-induced hepatic lipogenesis, fibrosis, and oxidative stress in high-fat diet-fed mice

Mulberry leaves (Morus alba L.) ameliorate obesity-induced hepatic lipogenesis, fibrosis, and oxidative stress in high-fat diet-fed mice

C/EBP-α ameliorates CCl4-induced liver fibrosis in mice through promoting apoptosis of hepatic stellate cells with little apoptotic effect on hepatocytes in vitro and in vivo

Therapeutic Impact of Berries (Morus Alba and Morus Rubra) Fruit Extract in the Regression of High-Fat Diet-Induced Cardiac Dysfunction in Rats

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