TGF-β isoforms in alcoholic liver disease

Santos, Rui M; Norton, Pamela A.; Esposti, Silvia Degli; Zern, Mark Α.

doi:10.1007/s005350050100

Cited by 26 publications

(19 citation statements)

References 30 publications

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“…These results indicated that the expression of TGF -beta 1 was highes in more active and advanced ALD patients. Santos et al [31] also demonstrated similar results in liver specimens. The presence of TGF-beta1 expression could be recognized as a risk factor for active and advanced alcoholic liver disease.…”

Section: Discussionsupporting

confidence: 72%

Quantitative analysis of transforming growth factor beta 1 mRNA in patients with alcoholic liver disease

Chen¹,

Li²,

Yu³

et al. 2002

WJG

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Section: Discussionsupporting

confidence: 72%

Quantitative analysis of transforming growth factor beta 1 mRNA in patients with alcoholic liver disease

Chen¹,

Li²,

Yu³

et al. 2002

WJG

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“…20 Increased levels of TGF-1 and its other isoforms have been shown to occur in animal models of hepatic fibrosis 21,22 and in patients with alcoholic liver disease. 23 Transgenic mice that overproduce the active form of TGF-developed significant fibrotic lesions in the liver and kidneys. 24 Recently, another line of transgenic mice that overexpress TGF-1 under the control of the C-reactive protein (CRP) promoter was developed.…”

Section: Activation Of Hscmentioning

confidence: 99%

Hepatic stellate cells: a target for the treatment of liver fibrosis

Zern

2000

Journal of Gastroenterology

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241

169

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Hepatic fibrosis is a wound-healing process that occurs when the liver is injured chronically. Hepatic stellate cells (HSC) are responsible for the excess production of extracellular matrix (ECM) components. The activation of HSC, a key issue in the pathogenesis of hepatic fibrosis, is mediated by various cytokines and reactive oxygen species released from the damaged hepatocytes and activated Kupffer cells. Therefore, inhibition of HSC activation and its related subsequent events, such as increased production of ECM components and enhanced proliferation, are crucial goals for intervention in the hepatic fibrogenesis cascade. This is especially true when the etiology is unknown or there is no established therapy for the cause of the chronic injury. This review explores the rationale for choosing HSC as a target for the pharmacological, molecular, and other novel therapeutics for hepatic fibrosis. One focus of this review is the inhibition of two cytokines, transforming growth factor-beta and platelet-derived growth factor, which are important in hepatic fibrogenesis. A number of new agents, such as Chinese herbal recipes and herbal extracts, silymarin, S-adenosyl-L-methionine, polyenylphosphatidylcholine, and pentoxifylline are also discussed.

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“…An early event in the development of liver fibrosis is the activation of hepatic stellate cells (HSCs), the major cell type responsible for increased synthesis of extracellular matrix proteins (5). An elevated level of transforming growth factor ␤1 (TGF-␤1) is also observed in the damaged liver, and it has a close correlation with fibrogenic changes in HSCs and liver tissue (6)(7)(8). In addition, decreased matrix metalloproteinase 9 (MMP-9) expression was observed in alcoholic liver fibrosis (9).…”

mentioning

confidence: 99%

The Effector Protein BPE005 from Brucella abortus Induces Collagen Deposition and Matrix Metalloproteinase 9 Downmodulation via Transforming Growth Factor β1 in Hepatic Stellate Cells

et al. 2016

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The liver is frequently affected in patients with active brucellosis. In the present study, we identified a virulence factor involved in the modulation of hepatic stellate cell function and consequent fibrosis during Brucella abortus infection. This study assessed the role of BPE005 protein from B. abortus in the fibrotic phenotype induced on hepatic stellate cells during B. abortus infection in vitro and in vivo. We demonstrated that the fibrotic phenotype induced by B. abortus on hepatic stellate (LX-2) cells was dependent on BPE005, a protein associated with the type IV secretion system (T4SS) VirB from B. abortus. Our results indicated that B. abortus inhibits matrix metalloproteinase 9 (MMP-9) secretion through the activity of the BPE005-secreted protein and induces concomitant collagen deposition by LX-2 cells. BPE005 is a small protein containing a cyclic nucleotide monophosphate binding domain (cNMP) that modulates the LX-2 cell phenotype through a mechanism that is dependent on the cyclic AMP (cAMP)/protein kinase A (PKA) signaling pathway. Altogether, these results indicate that B. abortus tilts LX-2 cells to a profibrogenic phenotype employing a functional T4SS and the secreted BPE005 protein through a mechanism that involves the cAMP and PKA signaling pathway. Brucellosis is a worldwide zoonosis characterized by hepatomegaly, splenomegaly, and peripheral lymphadenopathy. It is a chronic and debilitating infection caused by Gram-negative facultative intracellular bacteria that infect domestic and wild animals and that can be transmitted to humans (1, 2). The frequency of liver involvement in active brucellosis ranges from 5% to 52% or more (1). However, although numerous studies have focused on brucellar liver histopathology (1), the pathogenic mechanisms of liver disease caused by Brucella have not been completely investigated at the molecular and cellular levels.Liver fibrosis is a wound-healing response to chronic hepatic injury, which may be caused by alcohol abuse, hepatitis virus infection, or nonalcoholic steatohepatitis, and it is characterized by an excessive accumulation of extracellular matrix proteins in the liver (3, 4). An early event in the development of liver fibrosis is the activation of hepatic stellate cells (HSCs), the major cell type responsible for increased synthesis of extracellular matrix proteins (5). An elevated level of transforming growth factor ␤1 (TGF-␤1) is also observed in the damaged liver, and it has a close correlation with fibrogenic changes in HSCs and liver tissue (6-8). In addition, decreased matrix metalloproteinase 9 (MMP-9) expression was observed in alcoholic liver fibrosis (9). This fibrogenic phenotype involves alterations in the balance of MMPs and their natural inhibitors-tissue inhibitors of metalloproteinases (TIMPs). In particular, MMP-2 and MMP-9 (gelatinase A and B, respectively) are important in regulating fibrogenesis and scar degradation. They can degrade a variety of collagens, including basement membrane (type IV collagen), denatured fibrillar...

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TGF-β isoforms in alcoholic liver disease

Cited by 26 publications

References 30 publications

Quantitative analysis of transforming growth factor beta 1 mRNA in patients with alcoholic liver disease

Quantitative analysis of transforming growth factor beta 1 mRNA in patients with alcoholic liver disease

Hepatic stellate cells: a target for the treatment of liver fibrosis

The Effector Protein BPE005 from Brucella abortus Induces Collagen Deposition and Matrix Metalloproteinase 9 Downmodulation via Transforming Growth Factor β1 in Hepatic Stellate Cells

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