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Periostin promotes hepatic fibrosis in mice by modulating hepatic stellate cell activation via αv integrin interaction.
- Source :
- Journal of Gastroenterology; Dec2016, Vol. 51 Issue 12, p1161-1174, 14p
- Publication Year :
- 2016
-
Abstract
- <bold>Background: </bold>Periostin is a matricellular protein that serves as a ligand for integrins and is required for tissue remodeling and fibrosis. We investigated the role of periostin in hepatic fibrosis and the mechanisms involved.<bold>Methods: </bold>Primary hepatic stellate cells (HSCs) and the HSC-immortalized cell line LX2 were used to study the profibrotic property of periostin and the interaction of periostin with integrins. Wild-type and periostin-deficient (periostin-/-) mice were subjected to two distinct models of liver fibrosis induced by hepatotoxic (carbon tetrachloride or thioacetamide) or cholestatic (3.5-diethoxycarbonyl-1.4-dihydrocollidine) injury.<bold>Results: </bold>Periostin expression in HSCs and LX2 cells increased in association with their activation. Gene silencing of periostin resulted in a significant reduction in the levels of profibrotic markers. In addition to enhanced cell migration in response to periostin, LX2 cells incubated on periostin showed significant induction of α-smooth muscle actin and collagen, indicating a profibrotic property. An antibody targeting αvβ5 and αvβ3 integrins suppressed cell attachment to periostin by 60 and 30 % respectively, whereas anti-α5β1 antibody had no effect. Consistently, αv integrin-silenced LX2 cells exhibited decreased attachment to periostin, with a significant reduction in the levels of profibrotic markers. Moreover, these profibrotic effects of periostin were observed in the mouse models. In contrast to extensive collagen deposition in wild-type mice, periostin-/- mice developed less noticeable hepatic fibrosis induced by hepatotoxic and cholestatic liver injury. Accordingly, the profibrotic markers were significantly reduced in periostin-/- mice.<bold>Conclusion: </bold>Periostin exerts potent profibrotic activity mediated by αv integrin, suggesting the periostin-αv integrin axis as a novel therapeutic target for hepatic fibrosis. [ABSTRACT FROM AUTHOR]
- Subjects :
- HEPATIC fibrosis
PERIOSTIN
KUPFFER cells
INTEGRINS
LABORATORY mice
THERAPEUTICS
CELL metabolism
ANIMAL experimentation
BIOCHEMISTRY
CELL adhesion molecules
CELL culture
CELLS
CELL motility
CHOLESTASIS
DISEASE susceptibility
GENETIC techniques
CIRRHOSIS of the liver
PHENOMENOLOGY
MICE
RATS
DISEASE complications
PHYSIOLOGY
Subjects
Details
- Language :
- English
- ISSN :
- 09441174
- Volume :
- 51
- Issue :
- 12
- Database :
- Complementary Index
- Journal :
- Journal of Gastroenterology
- Publication Type :
- Academic Journal
- Accession number :
- 119755164
- Full Text :
- https://doi.org/10.1007/s00535-016-1206-0