Review article: the signalling and functional role of the extracellular matrix in the development of liver fibrosis

2020 ◽  
Vol 52 (1) ◽  
pp. 85-97 ◽  
Author(s):  
Ida Falk Villesen ◽  
Samuel Joseph Daniels ◽  
Diana Julie Leeming ◽  
Morten Asser Karsdal ◽  
Mette Juul Nielsen
2017 ◽  
Vol 312 (3) ◽  
pp. G219-G227 ◽  
Author(s):  
Leonie Beljaars ◽  
Sara Daliri ◽  
Christa Dijkhuizen ◽  
Klaas Poelstra ◽  
Reinoud Gosens

WNT-5A is a secreted growth factor that belongs to the noncanonical members of the Wingless-related MMTV-integration family. Previous studies pointed to a connection between WNT-5A and the fibrogenic factor TGF-β warranting further studies into the functional role of WNT-5A in liver fibrosis. Therefore, we studied WNT-5A expressions in mouse and human fibrotic livers and examined the relation between WNT-5A and various fibrosis-associated growth factors, cytokines, and extracellular matrix proteins. WNT-5A gene and protein expressions were significantly increased in fibrotic mouse and human livers compared with healthy livers. Regression or therapeutic intervention in mice resulted in decreased hepatic WNT-5A levels paralleled by lower collagen levels. Immunohistochemical analysis showed WNT-5A staining in fibrotic septa colocalizing with desmin staining indicating WNT-5A expression in myofibroblasts. In vitro studies confirmed WNT-5A expression in this cell type and showed that TGF-β significantly enhanced WNT-5A expression in contrast to PDGF-BB and proinflammatory cytokines IL-1β and TNF-α. Additionally, TGF-β induces the expression of the WNT receptors FZD2 and FZD8. After silencing of WNT-5A, reduced levels of collagen type I, vimentin, and fibronectin in TGF-β-stimulated myofibroblasts were measured compared with nonsilencing siRNA-treated controls. Interestingly, the antifibrotic cytokine IFNγ suppressed WNT-5A in vitro and in vivo. IFNγ-treated fibrotic mice showed significantly less WNT-5A expression compared with untreated fibrotic mice. In conclusion, WNT-5A paralleled collagen I levels in fibrotic mouse and human livers. WNT-5A expression in myofibroblasts is induced by the profibrotic factor TGF-β and plays an important role in TGF-β-induced regulation of fibrotic matrix proteins, whereas its expression can be reversed upon treatment, both in vitro and in vivo. NEW & NOTEWORTHY This study describes the localization and functional role of WNT-5A in human and mouse fibrotic livers. Hepatic WNT-5A expression parallels collagen type I expression. In vivo and in vitro, the myofibroblasts were identified as the key hepatic cells producing WNT-5A. WNT-5A is under control of TGF-β and its activities are primarily profibrotic.


2011 ◽  
Vol 112 (1) ◽  
pp. 318-329 ◽  
Author(s):  
Kohei Hamamoto ◽  
Satoko Yamada ◽  
Akemi Hara ◽  
Tsutomu Kodera ◽  
Masaharu Seno ◽  
...  

Tequio ◽  
2018 ◽  
Vol 1 (2) ◽  
pp. 79-84
Author(s):  
Osiris G Ildefonso García ◽  
Alma Aurora Ramírez Hernández ◽  
Jovito César Santos Álvarez ◽  
Juan M Velázquez Enriquez ◽  
Gabriel Carrasco Torres ◽  
...  

Liver fibrosis affects both the amount and the composition of the extracellular matrix. This process may occur during chronic liver disease characterized by hepato biliary disease or inflammation. There is now considerable evidence to support the role of the hepatic stellar cells (HSC) as the main matrix producing cells in fibrogenesis. The focus of this review is to provide insight into hepatic stellar cells in the fibrogenic process.


Fermentation ◽  
2019 ◽  
Vol 5 (2) ◽  
pp. 41 ◽  
Author(s):  
Vasiliki Lolou ◽  
Mihalis I. Panayiotidis

Scientific and commercial interest of probiotics, prebiotics and their effect on human health and disease has increased in the last decade. The aim of this review article is to evaluate the role of pro- and prebiotics on the normal function of healthy skin as well as their role in the prevention and therapy of skin disease. Lactobacilli and Bifidobacterium are the most commonly used probiotics and thought to mediate skin inflammation, treat atopic dermatitis (AD) and prevent allergic contact dermatitis (ACD). Probiotics are shown to decolonise skin pathogens (e.g., P. aeruginosa, S. aureus, A. Vulgaris, etc.) while kefir is also shown to support the immunity of the skin and treat skin pathogens through the production of antimicrobial substances and prebiotics. Finally, prebiotics (e.g., Fructo-oligosaccharides, galacto-oligosaccharides and konjac glucomannan hydrolysates) can contribute to the treatment of diseases including ACD, acne and photo aging primarily by enhancing the growth of probiotics.


2020 ◽  
Vol 102 ◽  
pp. 231-246 ◽  
Author(s):  
Franziska E. Uhl ◽  
Fuming Zhang ◽  
Robert A. Pouliot ◽  
Juan J. Uriarte ◽  
Sara Rolandsson Enes ◽  
...  

1984 ◽  
Vol 4 (1) ◽  
pp. 1-7 ◽  
Author(s):  
C C Howe

Previous work showed that tunicamycin suppresses glycosylation of laminin. In the present work, the role of glycosylation in the secretion of laminin and in the disulfide bonding of laminin subunits was studied, using tunicamycin to inhibit glycosylation. Tunicamycin inhibited extensively the secretion of laminin into culture medium and extracellular matrix even though the treated cells contained higher concentrations of laminin than the control cells. The laminin subunits synthesized in the presence of tunicamycin were disulfide bonded. Thus, suppression of glycosylation did not adversely affect disulfide bonding of the subunits, but did decrease the secretion of laminin. Glycosidases were also used to remove the carbohydrate of laminin to study the role of carbohydrate in the stability of laminin and in its interaction with another extracellular matrix component, heparin. The glycosidases removed about 73% of [3H]glucosamine. Both glycosidase-treated and untreated laminin were stable when incubated with cell lysate or culture medium. The glycosidase-treated laminin bound as efficiently as the untreated laminin to heparin. These results suggest that the presence of a carbohydrate moiety, at least at the level found in untreated laminin, is not essential in binding to heparin or in protecting laminin from proteolytic degradation in the cell or culture medium.


2021 ◽  
Vol 9 (8) ◽  
pp. 728-728
Author(s):  
Amit Khurana ◽  
Nilofer Sayed ◽  
Prince Allawadhi ◽  
Ralf Weiskirchen

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