Title |
Novel insights into the function and dynamics of extracellular matrix in liver fibrosis
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Published in |
American Journal of Physiology: Gastrointestinal & Liver Physiology, March 2015
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DOI | 10.1152/ajpgi.00447.2014 |
Pubmed ID | |
Authors |
Morten A Karsdal, Tina Manon-Jensen, Federica Genovese, Jacob H Kristensen, Mette J Nielsen, Jannie Marie B Sand, Niels-Ulrik B Hansen, Anne-Christine Bay-Jensen, Cecilie L Bager, Aleksander Krag, Andy Blanchard, Henrik Krarup, Diana J Leeming, Detlef Schuppan |
Abstract |
Emerging evidence suggests that altered components and post-translational modifications of proteins in the extracellular matrix (ECM) may both initiate and drive disease progression. The ECM is a complex grid consisting of multiple proteins most of which plays a vital role in containing the essential information needed for maintenance of a sophisticated structure anchoring the cells and sustaining normal function of tissues. Therefore, the matrix itself may be considered as a paracrine/endocrine entity, with more complex functions than previously appreciated. The aims of this review are to: 1) explore key structural and functional components of the ECM as exemplified by monogenetic disorders leading to severe pathologies; 2) discuss selected pathological post-translational modifications of ECM proteins resulting in altered functional (signalling) properties from the original structural proteins, and 3) discuss how these findings support the novel concept that an increasing number of components of the ECM harbour signalling functions that can modulate fibrotic liver disease. The ECM entails functions in addition to anchoring cells and modulating their migratory behaviour. Key ECM components and their post-translational modifications often harbour multiple domains with different signalling potential, in particular when modified during inflammation or wound healing. This signalling by the ECM should be considered as a paracrine/endocrine function as it affects cell phenotype, function, fate and finally tissue homeostasis. These properties should be exploited to establish novel biochemical markers and anti-fibrotic treatment strategies for liver fibrosis as well as other fibrotic diseases. |
X Demographics
Geographical breakdown
Country | Count | As % |
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United Kingdom | 1 | 100% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 1 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Denmark | 2 | <1% |
United Kingdom | 1 | <1% |
France | 1 | <1% |
Unknown | 267 | 99% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 61 | 23% |
Researcher | 43 | 16% |
Student > Master | 38 | 14% |
Student > Bachelor | 34 | 13% |
Student > Doctoral Student | 14 | 5% |
Other | 34 | 13% |
Unknown | 47 | 17% |
Readers by discipline | Count | As % |
---|---|---|
Biochemistry, Genetics and Molecular Biology | 64 | 24% |
Agricultural and Biological Sciences | 47 | 17% |
Medicine and Dentistry | 33 | 12% |
Engineering | 25 | 9% |
Pharmacology, Toxicology and Pharmaceutical Science | 17 | 6% |
Other | 24 | 9% |
Unknown | 61 | 23% |