Upregulation of matrilin-2 expression in murine hepatic stellate cells during liver injury has no effect on fibrosis formation and resolution.
Liver Int
; 35(4): 1265-73, 2015 Apr.
Article
em En
| MEDLINE
| ID: mdl-24905825
ABSTRACT
BACKGROUND & AIMS:
Matrilins are a family of four oligomeric adaptor proteins whose functions in extracellular matrix assembly during pathophysiological events still need to be explored in more detail. Matrilin-2 is the largest family member and the only matrilin expressed in the naive liver. Several studies demonstrate that matrilin-2 interacts with collagen I, fibronectin or laminin-111-nidogen-1 complexes. All these matrix components get upregulated during hepatic scar tissue formation. Therefore, we tested whether matrilin-2 has an influence on the formation and/or the resolution of fibrotic tissue in the mouse liver.METHODS:
Fibrosis was induced by infection with an adenovirus encoding cytochrome P450 2D6 (autoimmune liver damage) or by exposure to the hepatotoxin carbon tetrachloride. Fibrosis severity and matrilin-2 expression were assessed by immunohistochemistry. Hepatic stellate cells (HSCs) were isolated and analysed by immunocytochemistry and Transwell migration assays.RESULTS:
Both autoimmune as well as chemically induced liver damage led to simultaneous upregulation of matrilin-2 and collagen I expression. Discontinuation of carbon tetrachloride exposure resulted in concomitant dissolution of both proteins. Activated HSCs were the source of de novo matrilin-2 expression. Comparing wild type and matrilin-2-deficient mice, no differences were detected in fibronectin and collagen I upregulation and resolution kinetics as well as amount or location of fibronectin and collagen I production and degradation.CONCLUSIONS:
Our findings suggest that the absence of matrilin-2 has no effect on HSC activation and regression kinetics, synthetic activity, proliferative capacity, motility, or HSC apoptosis.Palavras-chave
Texto completo:
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Hepatite Autoimune
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Células Estreladas do Fígado
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Doença Hepática Induzida por Substâncias e Drogas
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Fígado
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Cirrose Hepática Experimental
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Liver Int
Ano de publicação:
2015
Tipo de documento:
Article