The antifibrogenic effect of (−)-epigallocatechin gallate results from the induction of de novo synthesis of glutathione in passaged rat hepatic stellate cells

Fu, Yumei; Zhou, Yajun; Zheng, Shizhong; Chen, Anping

doi:10.1038/labinvest.3700425

Cited by 57 publications

(38 citation statements)

References 47 publications

(54 reference statements)

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“…The most prominent was the extremely high expression of IGFBP-5, which is known to be the most abundantly expressed protein in activated HSC. In addition, IGFBP-7 is obviously detected in these cells, whereas a smaller induction is seen for IGFBP-4, -6 and -3 [6] . The growth-promoting and metabolic activities of IGF-1 and -2 are modulated by the family of IGFBPs [23] .…”

Section: Discussionmentioning

confidence: 95%

“…In recent studies, HSC were the primary source of excess ECM assembly in liver fibrosis [5] . During the development of liver fibrosis, HSC undergo a process of activation, resulting in the expression of ECM, reduced retinoid storage capability and transdifferentiation to a myofibroblast-like phenotype which is characterized by expression of α-smooth muscle actin (α-SMA) [6] . Fibrotic changes result in structural changes and lead to reconstruction of hepatic lobules, dysfunction of liver bioactivity, and even death.…”

Section: Introductionmentioning

confidence: 99%

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Insulin-like growth factor binding protein-7 induces activation and transdifferentiation of hepatic stellate cells in vitro

Liu¹,

Huang²,

Zhang³

et al. 2009

WJG

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AIM:To investigate the role of insulin-like growth factor binding protein-7 (IGFBP-7) in the activation and transdifferentiation of hepatic stellate cells (HSC) in vitro . METHODS:Rat HSC-T6 cells were cultured in separate dishes and treated with various concentration of transforming growth factor (TGF)-β1, IGFBP-7 or anti-IGFBP-7 antibody for 24 h. The supernatant or a cytoplasm suspension was obtained from cultured HSC, followed by transfer of cells to form cell-coated dishes. Immunocytochemistry and Western blotting were used to analyze the expression of IGFBP-7 induced by TGF-β1 and the level of fibronectin, collagen Ⅰ and α-smooth muscle actin (SMA). The pro-apoptotic effect of anti-IGFBP-7 antibody was determined by flow cytometry. RESULTS:Immunocytochemistry and Western blotting revealed that the expression of IGFBP-7 in TGF-β1 treated HSC was significantly up-regulated compared to that in the control group. In addition, fibronectin, c o l l a g e n Ⅰ a n d α-S M A a l s o s h o w e d e n h a n c e d expression in accordance with the transdifferentiation process in a dose-dependent manner to some extent. Moreover, flow cytometry suggested that anti-IGFBP-7 antibody induced apoptosis of activated HSC, which is responsible for the development of liver fibrosis, and may represent a novel pathway and target for therapeutic intervention.CONCLUSION: IGFBP-7 showed increased expression in activated HSC and played an important role in the activation and transdifferentiation process of HSC. Anti-IGFBP-7 antibody may ameliorate liver fibrogenesis.

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Section: Discussionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

Insulin-like growth factor binding protein-7 induces activation and transdifferentiation of hepatic stellate cells in vitro

Liu¹,

Huang²,

Zhang³

et al. 2009

WJG

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“…In addition, EGCG suppresses the proliferation of hepatic stellate cells and production of extracellular matrix in the hepatic fibrosis (19)(20)(21). Yumei et al reported that EGCG induced the de novo synthesis of glutathione and antifibrogenic effects in passaged rat hepatic stellate cells (22,23).…”

Section: Discussionmentioning

confidence: 99%

Epigallocatechin-3-gallate improves nonalcoholic steatohepatitis model mice expressing nuclear sterol regulatory element binding protein-1c in adipose tissue

Ueno

Torimura²,

Nakamura³

et al. 2009

Int J Mol Med

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Abstract. We examined whether or not epigallocatechin-3-gallate (EGCG) improves liver injury of nonalcoholic steatohepatitis (NASH) model mice expressing nuclear sterol regulatory element-binding protein 1c in adipose tissue. nSREBP-1c transgenic C57BL6 mice aged 30 weeks were divided into group 1 (no treatment), group 2 (ascorbic acid alone), group 3 (ascorbic acid and 0.05% EGCG), and group 4 (ascorbic acid and 0.1% EGCG). At 42 weeks, we performed measurement of liver weight to body weight, biochemical assays, morphometry of liver specimens, immunohistochemistry for 8-hydro-2'-deoxyguanosine (8-OhdG), and Western blotting for insulin and TNF-· signalings. Ratio of liver weight to body weight in the high dose EGCG-treated group (group 4) was significantly lower than those of groups 1 and 2 (p<0.05 and <0.01, respectively). Blood ALT, glucose, total cholesterol, and triglyceride levels of group 4 were significantly low compared with those of the EGCGnon-treated group (groups 1 and 2) (p<0.05, respectively). The degrees of steatosis, inflammation, ballooning hepatocytes and Mallory-Denk bodies in group 4 significantly improved compared with those in other groups (p<0.05, respectively). The 8-OhdG immunolocalization in liver tissues of the group 4 obviously decreased compared with those of groups 2 and 3. For Western blotting, the expressions of insulin receptor substrate-1 (IRS-1) and phosphorylated IRS-1 (pIRS-1) in liver tissues of group 4 increased compared with those of groups 2 and 3. On the other hand, the expressions of pAkt, pIKKß and pNF-κB decreased compared with those of groups 2 and 3. From these results, EGCG reduces inflammation, insulin resistance and oxidative stress, and suppresses liver injury in nSREBP-1c transgenic mice. IntroductionAlthough the obesity epidemic is a worldwide phenomenon, the severity of the epidemic differs greatly from region to region. The prevalence of obesity among Japanese adults is 3.4% in males and 3.8% in females, and is around one tenth of that in the USA (1). In addition, currently in Japan almost 30% of adult males and females over 50 years old are obese. This rising incidence of obesity parallels the dramatic increase in fatty liver in these age groups. Based on annual health checks, the prevalence of fatty liver diagnosed by ultrasonography increased from 10% in 1980 to 20-40% in 2000 among adults. Thus, nonalcoholic fatty liver disease (NAFLD) is now emerging as the most common liver disease in Japan (2,3). The recent worldwide rise in the number of patients with nonalcoholic steatohepatitis (NASH) tends to parallel the increase in metabolic syndrome, which includes obesity, type 2 diabetes and hyperlipidemia (4).NAFLD mainly comprises of simple steatosis that is considered benign, however some patients have nonalcoholic steatohepatitis (NASH), which is a clinicopathological entity characterized by the development of hepatic histological changes resembling those induced by excessive alcohol intake that occur in the absence of alcohol abuse (5). Some patients w...

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“…cells play a central role in hepatic fibrosis (21), and epigallocatechin gallate, the major green tea polyphenol catechin, has been shown to inhibit collagen production in these cells (17). It has also been demonstrated that epigallocatechin gallate inhibits activation of these cells by suppressing Rho signaling, suggesting its therapeutic potential in the setting of liver fibrosis (8).…”

Section: Figmentioning

confidence: 99%

The anti-fibrotic effect of green tea with a high catechin content in the galactosamine-injured rat liver

et al. 2007

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Previously, we reported that the oral administration of green tea rich in catechins restored levels of several biomarkers increasing in galactosamine-treated rats to nearly control values. These biomarkers included serum transaminase activities, serum concentrations of tumor necrosis factor-α and interleukin 1-β, and the hepatic mRNA expression of these inflammatory cytokines. In the present study, we examined possible anti-fibrotic effects of green tea in galactosamine-induced hepatitis. The results of the reverse transcription and polymerase chain reaction indicated that the increase in gene expression of the α1 chain of collagen type 1 and transforming growth factor β-1 in the injured liver 24 h post-injection of galactosamine was suppressed by the administration of green tea. Masson's trichrome staining demonstrated that the extent of fibrogenesis after 14 days was greater in the galactosamine-injured livers not treated with green tea than the treated ones. These results suggest that the drinking of green tea with a high catechin content may help to prevent and/or attenuate the development of fibrosis in hepatitis.

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The antifibrogenic effect of (−)-epigallocatechin gallate results from the induction of de novo synthesis of glutathione in passaged rat hepatic stellate cells

Cited by 57 publications

References 47 publications

Insulin-like growth factor binding protein-7 induces activation and transdifferentiation of hepatic stellate cells in vitro

Insulin-like growth factor binding protein-7 induces activation and transdifferentiation of hepatic stellate cells in vitro

Epigallocatechin-3-gallate improves nonalcoholic steatohepatitis model mice expressing nuclear sterol regulatory element binding protein-1c in adipose tissue

The anti-fibrotic effect of green tea with a high catechin content in the galactosamine-injured rat liver

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