Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0239946 (liver fibrosis)
 8,268 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Liver fibrosis occurs as a consequence of the transdifferentiationof hepatic stellate cells into myofibroblasts and is associated with an increased expression and activation of transforming growth factor (TGF)-beta1. This pluripotent, profibrogenic cytokine stimulates matrix synthesis and decreases matrix degradation, resulting in fibrosis. Thus, blockade of synthesis or sequestering of mature TGF-beta1 is a primary target for the development of antifibrotic approaches. The purpose of this study was to investigate whether the administration of adenoviruses constitutively expressing an antisense mRNA complementary to the 3' coding sequence of TGF-beta1 is able to suppress the synthesis of TGF-beta1 in culture-activated hepatic stellate cells. We demonstrate that the adenoviral vehicle directs high-level expression of the transgene and proved that the transduced antisense is biologically active by immunoprecipitation, Western blot, quantitative TGF-beta1 ELISA, and cell proliferation assays. Additionally, the biological function of the transgene was confirmed by analysis of differential activity of TGF-beta1-responsive genes using cell ELISA, Northern blotting, and by microarray technology, respectively. Furthermore, we examined the effects of that transgene on the expression of TGF-beta2, TGF-beta3, collagen type alpha1(I), latent transforming growth factor binding protein 1, types I and II TGF-beta receptors, and alpha-smooth muscle actin. Our results indicate that the administration of antisense mRNA offers a feasible approach to block autocrine TGF-beta1 signaling in hepatic stellate cells and may be useful and applicable in future to the treatment of fibrosis in chronic liver diseases.
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PMID:Adenoviral delivery of an antisense RNA complementary to the 3' coding sequence of transforming growth factor-beta1 inhibits fibrogenic activities of hepatic stellate cells. 1211 16

AII (angiotensin II) is a vasoactive peptide that plays an important role in the development of liver fibrosis mainly by regulating profibrotic cytokine expression such as TGF-beta (transforming growth factor-beta). Activated HSCs (hepatic stellate cells) are the major cell type responsible for ECM (extracellular matrix) deposition during liver fibrosis and are also a target for AII and TGF-beta actions. Here, we studied the effect of AII on the mRNA levels of TGF-beta isoforms in primary cultures of rat HSCs. Both quiescent and activated HSCs were stimulated with AII for different time periods, and mRNA levels of TGF-beta1, TGF-beta2 and TGF-beta3 isoforms were evaluated using RNaseI protection assay. The mRNA levels of all TGF-beta isoforms, particularly TGF-beta2and TGF-beta3, were increased after AII treatment in activated HSCs. In addition, activated HSCs were able to produce active TGF-beta protein after AII treatment. The mRNA expression of TGF-beta isoforms induced by AII required both ERK1/2 and Nox (NADPH oxidase) activation but not PKC (protein kinase C) participation. ERK1/2 activation induced by AII occurs via AT1 receptors, but independently of either PKC and Nox activation or EGFR (epidermal growth factor receptor) transactivation. Interestingly, AII has a similar effect on TGF-beta expression in quiescent HSCs, although it has a smaller but significant effect on ERK1/2 activation in these cells.
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PMID:Angiotensin II increases mRNA levels of all TGF-beta isoforms in quiescent and activated rat hepatic stellate cells. 2055 91

The liver fluke Clonorchis sinensis (Digenea) is a high-risk parasite that causes serious diseases such as cirrhosis, carcinogenic liver damage and clonorchiasis in East Asia. This study was conducted to evaluate the relationship between stress/endocrine hormones and inflammation induced by infection as well as the expression of heat shock proteins (hsp-27, hsp-90), cox-2 and cytokines in the livers of hamsters infected with C. sinensis. The average body weight of infected hamsters decreased up to 25% compared with that of the control group, and bile duct hyperplasia with inflammation, liver fibrosis and hepatic necrosis were observed in C. sinensis-infected livers. The expression of hsp-27, hsp-90, and cox-2 was significantly increased in the livers of C. sinensis-infected hamsters compared with the control group. Moreover, the expression levels of inflammatory cytokines (IL-1beta, IL-2, TGF-beta2 and IFN-alpha1) were markedly increased in the livers of the infected group compared with those of the control group. Consistently, plasma IL-3 and IL-6 levels gradually increased during the infection period, and the concentration levels of testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH), corticosterone, and adrenocorticotropic hormone (ACTH) in C. sinensis-infected hamsters increased over 25%, compared with those of the uninfected normal group. These results demonstrate that C. sinensis infection may increase the expression of hsp27, hsp90 and cox-2 as well as it may cause periductal fibrosis, chronic inflammation and hepatic necrosis in the liver. Furthermore, the results indicate that C. sinensis infection induces not only stress-induced hormone imbalance but also the sustained secretion of inflammatory cytokines through chronic stress/stimuli.
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PMID:The characteristics of the expression of heat shock proteins and COX-2 in the liver of hamsters infected with Clonorchis sinensis, and the change of endocrine hormones and cytokines. 2332 6