scholarly journals Evaluation of methanolic extract of Phragmites karka on carbon tetrachloride-induced liver fibrosis in rat

2017 ◽  
Vol 12 (3) ◽  
pp. 276 ◽  
Author(s):  
Atta Ur Rehman ◽  
Manal Liaqat ◽  
Rabia Asghar ◽  
Nawazish-i-Husain Syed
Keyword(s):  
Extracellular Matrix ◽  
Liver Fibrosis ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Smooth Muscle Actin ◽  
Serum Levels ◽  
Matrix Deposition ◽  
Male Wistar Rats ◽  
Phragmites Karka ◽  
Extracellular Matrix Deposition

<p class="Abstract"><em>Phragmites karka</em> has been reported for its anti-inflammatory and analgesic activities. Here, extracts of leaf and rhizome of the plant were individually investigated in CCl<sub>4</sub>-induced hepatofibrosis in male Wistar rats by administering CCl<sub>4</sub> intraperitoneally biweekly for 6 weeks.  Afterwards the animals were investigated for liver fibrosis at biochemical, molecular and histological levels, and it showed a profound increase (p&lt;0.001) in elevation of serum levels of transaminases, γ-glutamyl transpeptidase, mRNA expression of α smooth muscle actin, collagen and transforming growth factor beta (TGFβ), and extracellular matrix deposition and perilobular necrosis. Both extracts markedly (p&lt;0.001) decreased the elevated levels of these markers. Histopathological investigations also substantiated the above results by exhibiting a decreased in extracellular matrix deposition in post-treatment animals. In conclusion, both extracts had substantially modified the biochemical and molecular markers of liver fibrosis, in addition to histological improvement in architecture of liver.</p>

scholarly journals Therapeutic Effect of Dunaliella salina Microalgae on Thioacetamide- (TAA-) Induced Hepatic Liver Fibrosis in Rats: Role of TGF-β and MMP9

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Farouk K. El-Baz ◽  
Abeer Salama ◽  
Rania A. A. Salama
Keyword(s):  
Liver Fibrosis ◽  
Transforming Growth Factor Beta ◽  
Dunaliella Salina ◽  
Transforming Growth Factor ◽  
Smooth Muscle Actin ◽  
Elevated Serum ◽  
Serum Levels ◽  
Dependent Manner ◽  
Necrosis Factor Alpha ◽  
Liver Histopathology

Liver fibrosis represents a serious global health-care problem and is the outcome of many chronic liver diseases, cirrhosis, hepatitis, and toxin accumulation. The present study aimed to evaluate the antifibrotic curative effect of Dunaliella salina (D. salina) on thioacetamide- (TAA-) induced liver fibrosis in rats. Liver fibrosis was induced by TAA (200mg/kg; i.p.) twice per week for 6 weeks. D. salina was given orally (100 and 200 mg/kg) and silymarin was given orally (100 mg/kg) daily, for 4 weeks after TAA. Serum transaminase activities, liver inflammatory cytokines, fibrotic biomarkers, and liver histopathology were assessed. TAA significantly (p<0.05) elevated serum activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) and serum levels of total bilirubin, tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and transforming growth factor-beta (TGF-β) with a reduction in albumin. In addition, TAA increased hepatic contents of collagen I, a-smooth muscle actin (α-SMA), and tissue inhibitors of metalloproteinase (TIMP-1), reduced matrix metalloproteinase 9 (MMP9), and finally produced marked degeneration and fibrosis of hepatocytes. Treatment with D. salina or silymarin improved the histological feature of hepatocytes and ameliorated the deleterious effects of TAA in a dose-dependent manner. Based on these results, it could be concluded that the use of D. salina could be assigned for liver fibrosis treatment via its anti-inflammatory and antifibrotic properties.

Carvacrol Ameliorates Transforming Growth Factor-β1-Induced Extracellular Matrix Deposition and Reduces Epithelial-Mesenchymal Transition by Regulating The Phosphatidylinositol 3-Kinase/Protein Kinase B Pathway In Hk-2 Cells

2021 ◽  
Vol 19 (4) ◽  
pp. 501-507
Author(s):  
Yunhe Gu ◽  
Peiyao Guo ◽  
Guangbiao Xu
Keyword(s):  
Extracellular Matrix ◽  
Growth Factor ◽  
Renal Fibrosis ◽  
Transforming Growth Factor ◽  
Epithelial Mesenchymal Transition ◽  
Transforming Growth Factor Β1 ◽  
Mesenchymal Transition ◽  
Matrix Deposition ◽  
Extracellular Matrix Deposition ◽  
Dose Dependent

Transforming growth factor-β1 promotes excessive extracellular matrix deposition and epithelial-mesenchymal transition of tubular epithelial cells, thus stimulating the progression of renal fibrosis. Carvacrol has been shown to alleviate cardiac and liver fibrosis and attenuate renal injury. However, the role of carvacrol on renal fibrosis has not been examined. First, measurements using Cell Counting Kit-8 showed that carvacrol reduced cell viability of tubular epithelial cell line HK-2 in a dose-dependent fashion. Second, transforming growth factor-β1 induced excessive extracellular matrix deposition in HK-2 cells with enhanced collagen I, collagen IV, and fibronectin expression. However, carvacrol decreased the expression of collagen I, collagen IV in a dose-dependent manner and fibronectin to attenuate the extracellular matrix deposition in HK-2. Third, carvacrol attenuated TGF-β1-induced decrease of E-cadherin and increase of snail, vimentin, and alpha-smooth muscle actin in HK-2 cells. Transforming growth factor-β1-induced increase in PI3K and AKT phosphorylation in HK-2 were also reversed by carvacrol. Collectively, carvacrol ameliorates renal fibrosis through inhibition of transforming growth factor-β1-induced extracellular matrix deposition and epithelial-mesenchymal transition of HK-2 cells, providing potential therapy for the treatment of renal fibrosis.

scholarly journals Hierarchical Coculture of Hepatocyte and Hepatic Non-Parenchymal Cells for Liver Fibrosis Studies in vitro

2020 ◽  
Author(s):  
Qiao You Lau ◽  
Fuad Gandhi Torizal ◽  
Marie Shinohara ◽  
Yasuyuki Sakai
Keyword(s):  
Growth Factor ◽  
Liver Fibrosis ◽  
Oxygen Tension ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Smooth Muscle Actin ◽  
Liver Sinusoidal Endothelial Cell ◽  
Type I ◽  
Parenchymal Cells

During chronic liver injury, inflammation leads to the development of liver fibrosis&mdash; particularly due to the activation of hepatic stellate cells (HSCs). However, the involvement of inflammatory cytokines in HSC activation is unclear. Many existing in vitro liver models do not include these non-parenchymal cells (NPCs), and hence, do not represent the physiological relevance found in vivo. Herein, we demonstrated the hierarchical coculture of primary rat hepatocytes with NPCs such as the human-derived HSC line (LX-2) and the human-derived liver sinusoidal endothelial cell line (TMNK-1). The coculture tissue had higher albumin production and hepatic cytochrome P450 3A4 activity compared to the monoculture. We then further studied the effects of stimulation by both oxygen tension and key pro-fibrogenic cytokines, such as the transforming growth factor beta (TGF-&beta;), on HSC activation. Gene expression analysis revealed that lower oxygen tension and TGF-&beta;1 stimulation enhanced collagen type I, III, and IV, alpha-smooth muscle actin, platelet-derived growth factor, and matrix metallopeptidase expression from LX-2 cells in the hierarchical coculture after fibrogenesis induction. This hierarchical in vitro cocultured liver tissue could, therefore, provide an improved platform as a disease model for elucidating the interactions of various liver cell types and biochemical signals in liver fibrosis studies.

The anti-inflammatory and anti-fibrotic effects of tadalafil in thioacetamide-induced liver fibrosis in rats

2018 ◽  
Vol 96 (12) ◽  
pp. 1308-1317 ◽  
Author(s):  
Heba M. Mansour ◽  
Abeer A.A. Salama ◽  
Rania M. Abdel-Salam ◽  
Naglaa A. Ahmed ◽  
Noha N. Yassen ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Inflammatory Cytokines ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Smooth Muscle Actin ◽  
Interleukin 1 ◽  
Health Concern ◽  
Dependent Manner ◽  
Serum Transaminases ◽  
Anti Inflammatory

Liver fibrosis is a health concern that leads to organ failure mediated via production of inflammatory cytokines and fibrotic biomarkers. This study aimed to explore the protective effect of tadalafil, a phosphodiesterase-5 inhibitor, against thioacetamide (TAA)-induced liver fibrosis. Fibrosis was induced by administration of TAA (200 mg/kg, i.p.) twice weekly for 6 weeks. Serum transaminases activities, liver inflammatory cytokines, fibrotic biomarkers, and liver histopathology were assessed. TAA induced marked histopathological changes in liver tissues coupled with elevations in serum transaminases activities. Furthermore, hepatic content of nitric oxide and tumor necrosis factor-alpha, interleukin-6, and interleukin-1 beta were elevated, together with a reduction of interleukin-10 in the liver. In addition, TAA increased hepatic contents of transforming growth factor-beta, hydroxyproline, alpha-smooth muscle actin, and gene expression of collagen-1. Pretreatment with tadalafil protected against TAA-induced liver fibrosis, in a dose-dependent manner, as proved by the alleviation of inflammatory and fibrotic biomarkers. The effects of tadalafil were comparable with that of silymarin, a natural antioxidant, and could be assigned to its anti-inflammatory and anti-fibrotic properties.

Proteoglycans of uterine fibroids and keloid scars: similarity in their proteoglycan composition

2012 ◽  
Vol 443 (2) ◽  
pp. 361-368 ◽  
Author(s):  
David A. Carrino ◽  
Sam Mesiano ◽  
Nichole M. Barker ◽  
William W. Hurd ◽  
Arnold I. Caplan
Keyword(s):  
Extracellular Matrix ◽  
Connective Tissue ◽  
Transforming Growth Factor ◽  
Uterine Fibroids ◽  
Transforming Growth Factor Β ◽  
Structural Support ◽  
Normal Tissues ◽  
Matrix Deposition ◽  
Keloid Scars ◽  
Extracellular Matrix Deposition

Fibrosis is the formation of excess and abnormal fibrous connective tissue as a result of either a reparative or reactive process. A defining feature of connective tissue is its extracellular matrix, which provides structural support and also influences cellular activity. Two common human conditions that result from fibrosis are uterine fibroids (leiomyomas) and keloid scars. Because these conditions share a number of similarities and because their growth is due primarily to excessive extracellular matrix deposition, we compared the proteoglycans of uterine fibroids and keloid scars with corresponding normal tissues. Our analysis indicates that uterine fibroids and keloid scars contain higher amounts of glycosaminoglycans relative to normal myometrium and normal adult skin respectively. Proteoglycan composition is also different in the fibrotic tissues. Compared with unaffected tissues, uterine fibroids and keloid scars contain higher relative amounts of versican and lower relative amounts of decorin. There is also evidence for a higher level of versican catabolism in the fibrotic tissues compared with unaffected tissues. These qualitative and quantitative proteoglycan differences may play a role in the expansion of these fibroses and in their excessive matrix deposition and matrix disorganization, due to effects on cell proliferation, TGF (transforming growth factor)-β signalling and/or collagen fibril formation.

Transforming growth factor beta-induced Foxo3a acts as a profibrotic mediator in hepatic stellate cells

2020 ◽  
Author(s):  
Seung Jung Kim ◽  
Kyu Min Kim ◽  
Ji Hye Yang ◽  
Sam Seok Cho ◽  
Eun Hee Jeong ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Transforming Growth Factor Beta ◽  
Hepatic Stellate Cells ◽  
Transforming Growth Factor ◽  
Smooth Muscle Actin ◽  
Stellate Cells ◽  
Forkhead Transcription Factor ◽  
Hepatic Fibrogenesis ◽  
Duct Ligation ◽  
Nuclear Levels

Abstract Hepatic stellate cells (HSCs) are major contributors to hepatic fibrogenesis facilitating liver fibrosis. FoxO3a is a member of the forkhead transcription factor family, which mediates cell proliferation and differentiation. However, the expression and function of FoxO3a during HSC activation remain largely unknown. FoxO3a overexpression was related to fibrosis in patients, and its expression was colocalized with desmin or α-smooth muscle actin, representative HSC markers. We also observed upregulated FoxO3a levels in two animal hepatic fibrosis models, a carbon tetrachloride (CCl4)-injected model and a bile duct ligation model. In addition, TGF-β treatment in mouse primary HSCs or LX-2 cells elevated FoxO3a expression. When FoxO3a was upregulated by TGF-β in LX-2 cells, both the cytosolic and nuclear levels of FoxO3a increased. In addition, we found that the induction of FoxO3a by TGF-β was due to both transcriptional and proteasome-dependent mechanisms. Moreover, FoxO3a overexpression promoted TGF-β-mediated Smad activation. Furthermore, FoxO3a increased fibrogenic gene expression, which was reversed by FoxO3a knockdown. TGF-β-mediated FoxO3a overexpression in HSCs facilitated hepatic fibrogenesis, suggesting that FoxO3a may be a novel target for liver fibrosis prevention and treatment.

Possible roles for TGF beta 1 in the gastrulating chick embryo

1991 ◽  
Vol 99 (3) ◽  
pp. 617-626 ◽  
Author(s):  
E.J. Sanders ◽  
S. Prasad
Keyword(s):  
Extracellular Matrix ◽  
Chick Embryo ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Cell Phenotype ◽  
Tgf Beta ◽  
Fibronectin Receptor ◽  
Amino Terminal ◽  
Matrix Deposition ◽  
Mesenchymal Transformation

We have examined the immunocytochemical distribution of TGF beta 1 (transforming growth factor beta 1) in the gastrulating chick embryo, and have correlated the results with the ability of this factor to promote in vitro changes in the phenotype of mesoderm and epiblast cells. The findings, together with the demonstration that exogenous TGF beta 1 is also able to modulate extracellular matrix deposition by these cells in culture, are consistent with a role for this factor in the formation and morphogenesis of the early mesoderm. Immunofluorescence analysis, using an antibody to the amino-terminal fragment of TGF beta 1, indicates that this factor is located in, or between, cells of the medial epiblast, Hensen's node and primitive streak. At Hensen's node, cells of the hypoblast were also strongly labelled. Ingressed mesoderm cells, lateral to the streak, show considerably stronger and more diffuse labelling than the overlying epiblast cells. Although the fluorescent labelling appears to be associated with the extracellular matrix surrounding the mesoderm cells, it is not bound to hyaluronic acid, which is the preponderant molecule in the matrix at this time in development. When added exogenously to cultures of mesoderm cells growing with epithelial characteristics on fibronectin, TGF beta 1 effects an epithelial-mesenchymal transformation within 24 h. The reverse transformation is effected in mesoderm cells grown on laminin, while the epiblast cell phenotype is not affected by this treatment regardless of the substratum. TGF beta 1 is also able to down-regulate the deposition of fibronectin by mesoderm cells grown on fibronectin and of epiblast cells grown on laminin, but up-regulate fibronectin deposition by mesoderm on laminin. Similar substratum-dependent changes are seen in laminin deposition, which is down-regulated in mesoderm on laminin and up-regulated in epiblast on laminin. No effect on laminin deposition is seen in either cell type grown on fibronectin. Expression of the fibronectin receptor is also down-regulated by TGF beta 1 in mesoderm cells grown on fibronectin, and this may explain the decreased deposition of fibronectin associated with these cells under these conditions. We suggest that these results are consistent with a reinforcing role for TGF beta 1 in the transformation that results in the emergence of mesoderm cells at gastrulation. This factor may also be involved in the maintenance of the fibroblastic phenotype of the mesoderm cells after their ingression, by effects on the expression of receptors for extracellular matrix and on the deposition of matrix by these cells during their early morphogenesis.

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