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Periostin promotes hepatic fibrosis in mice by modulating hepatic stellate cell activation via αv integrin interaction
- Source :
- Journal of Gastroenterology. 51:1161-1174
- Publication Year :
- 2016
- Publisher :
- Springer Science and Business Media LLC, 2016.
-
Abstract
- 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. 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. 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. Periostin exerts potent profibrotic activity mediated by αv integrin, suggesting the periostin–αv integrin axis as a novel therapeutic target for hepatic fibrosis.
- Subjects :
- 0301 basic medicine
Pathology
medicine.medical_specialty
biology
Chemistry
Cell adhesion molecule
Matricellular protein
Integrin
Gastroenterology
Periostin
Hepatic stellate cell activation
03 medical and health sciences
030104 developmental biology
0302 clinical medicine
030220 oncology & carcinogenesis
Hepatic stellate cell
medicine
Cancer research
biology.protein
Hepatic fibrosis
Myofibroblast
Subjects
Details
- ISSN :
- 14355922 and 09441174
- Volume :
- 51
- Database :
- OpenAIRE
- Journal :
- Journal of Gastroenterology
- Accession number :
- edsair.doi...........264ce0455ddfb936497fefe8348e0c03