Periostin Facilitates Skin Sclerosis via PI3K/Akt Dependent Mechanism in a Mouse Model of Scleroderma
Open Access
- 24 July 2012
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 7 (7), e41994
- https://doi.org/10.1371/journal.pone.0041994
Abstract
Periostin, a novel matricellular protein, is recently reported to play a crucial role in tissue remodeling and is highly expressed under fibrotic conditions. This study was undertaken to assess the role of periostin in scleroderma. Using skin from patients and healthy donors, the expression of periostin was assessed by immunohistochemistry and immunoblotting analyses. Furthermore, we investigated periostin−/− (PN−/−) and wild-type (WT) mice to elucidate the role of periostin in scleroderma. To induce murine cutaneous sclerosis, mice were subcutaneously injected with bleomycin, while untreated control groups were injected with phosphate-buffered saline. Bleomycin-induced fibrotic changes were compared in PN−/− and WT mice by histological analysis as well as by measurements of profibrotic cytokine and extracellular matrix protein expression levels in vivo and in vitro. To determine the downstream pathway involved in periostin signaling, receptor neutralizing antibody and signal transduction inhibitors were used in vitro. Elevated expression of periostin was observed in the lesional skin of patients with scleroderma compared with healthy donors. Although WT mice showed marked cutaneous sclerosis with increased expression of periostin and increased numbers of myofibroblasts after bleomycin treatment, PN−/− mice showed resistance to these changes. In vitro, dermal fibroblasts from PN−/− mice showed reduced transcript expression of alpha smooth actin and procollagen type-I alpha 1 (Col1α1) induced by transforming growth factor beta 1 (TGFβ1). Furthermore, recombinant mouse periostin directly induced Col1α1 expression in vitro, and this effect was inhibited by blocking the αv integrin-mediated PI3K/Akt signaling either with anti-αv functional blocking antibody or with the PI3K/Akt kinase inhibitor LY294002. Periostin plays an essential role in the pathogenesis of Bleomycin-induced scleroderma in mice. Periostin may represent a potential therapeutic target for human scleroderma.Keywords
This publication has 50 references indexed in Scilit:
- Periostin in fibrillogenesis for tissue regeneration: periostin actions inside and outside the cellCellular and Molecular Life Sciences, 2011
- Enhanced Epithelial-Mesenchymal Transition-like Phenotype in N-Acetylglucosaminyltransferase V Transgenic Mouse Skin Promotes Wound HealingOnline Journal of Public Health Informatics, 2011
- Roles of epithelial cell-derived periostin in TGF-β activation, collagen production, and collagen gel elasticity in asthmaProceedings of the National Academy of Sciences of the United States of America, 2010
- The matricellular protein CCN1 induces fibroblast senescence and restricts fibrosis in cutaneous wound healingNature, 2010
- Spatiotemporal expression of periostin during skin development and incisional wound healing: lessons for human fibrotic scar formationJournal of Cell Communication and Signaling, 2010
- The many facets of the matricelluar protein periostin during cardiac development, remodeling, and pathophysiologyJournal of Cell Communication and Signaling, 2009
- Functions and mechanisms of action of CCN matricellular proteinsThe International Journal of Biochemistry & Cell Biology, 2009
- Functional role of periostin in development and wound repair: implications for connective tissue diseaseJournal of Cell Communication and Signaling, 2008
- Periostin is essential for cardiac healingafter acute myocardial infarctionThe Journal of Experimental Medicine, 2008
- Periostin regulates collagen fibrillogenesis and the biomechanical properties of connective tissuesJournal of Cellular Biochemistry, 2007