Plasma transforming growth factor-? (TGF-?) levels in hepatic fibrosis Duke University Medical Center, Durham, NC, Department of Medicine, *Department of Pathology, #Department of Radiation Oncology

Hepatology ◽  
1995 ◽  
Vol 22 (4) ◽  
pp. A287 ◽  
2002 ◽  
Vol 36 ◽  
pp. 69
Author(s):  
Javier Crespo ◽  
Amalia Cayon ◽  
Marta Mayorga ◽  
Agustin Dominguez-Diez ◽  
Manuel Hernandez-Guerra ◽  
...  

Cells ◽  
2019 ◽  
Vol 8 (11) ◽  
pp. 1356 ◽  
Author(s):  
Milito ◽  
Brancaccio ◽  
D’Argenio ◽  
Castellano

Liver fibrosis is a pathophysiologic process involving the accumulation of extracellular matrix proteins as collagen deposition. Advanced liver fibrosis can evolve in cirrhosis, portal hypertension and often requires liver transplantation. At the cellular level, hepatic fibrosis involves the activation of hepatic stellate cells and their transdifferentiation into myofibroblasts. Numerous pro-fibrogenic mediators including the transforming growth factor-β1, the platelet-derived growth factor, endothelin-1, toll-like receptor 4, and reactive oxygen species are key players in this process. Knowledge of the cellular and molecular mechanisms underlying hepatic fibrosis development need to be extended to find novel therapeutic strategies. Antifibrotic therapies aim to inhibit the accumulation of fibrogenic cells and/or prevent the deposition of extracellular matrix proteins. Natural products from terrestrial and marine sources, including sulfur-containing compounds, exhibit promising activities for the treatment of fibrotic pathology. Although many therapeutic interventions are effective in experimental models of liver fibrosis, their efficacy and safety in humans are largely unknown. This review aims to provide a reference collection on experimentally tested natural anti-fibrotic compounds, with particular attention on sulfur-containing molecules. Their chemical structure, sources, mode of action, molecular targets, and pharmacological activity in the treatment of liver disease will be discussed.


2003 ◽  
Vol 39 (5) ◽  
pp. 742-748 ◽  
Author(s):  
Hiroki Kondou ◽  
Sotaro Mushiake ◽  
Yuri Etani ◽  
Yoko Miyoshi ◽  
Toshimi Michigami ◽  
...  

2009 ◽  
Vol 297 (4) ◽  
pp. G762-G767 ◽  
Author(s):  
William Kemp ◽  
Andrew Kompa ◽  
Arintaya Phrommintikul ◽  
Chandana Herath ◽  
Jia Zhiyuan ◽  
...  

The influence of circulating urotensin II (UII) on liver disease and portal hypertension is unknown. We aimed to evaluate whether UII executes a pathogenetic role in the development of hepatic fibrosis and portal hypertension. UII was administered by continuous infusion over 4 wk in 20 healthy rats divided into three treatment groups, controls (saline, n = 7), low dose (UII, 1 nmol·kg−1·h−1, n = 8), and high dose (UII, 3 nmol·kg−1·h−1, n = 5). Hemodynamic parameters and morphometric quantification of fibrosis were assessed, and profibrotic cytokines and fibrosis markers were assayed in hepatic tissue. UII induced a significant dose-dependent increase in portal venous pressure (5.8 ± 0.4, 6.4 ± 0.3, and 7.6 ± 0.7, respectively, P = 0.03). High-dose UII infusion was associated with an increase in hepatic transcript for transforming growth factor-β ( P < 0.05) and platelet-derived growth factor-β ( P = 0.06). Liver tissue hydroxyproline was elevated in the high-dose group ( P < 0.05). No systemic hemodynamic alterations were noted. We concluded that UII infusion elevates portal pressure and induces hepatic fibrosis in normal rats. This response may be mediated via induction of fibrogenic cytokines. These findings have pathophysiological implications in human liver disease where increased plasma UII levels have been observed.


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