Periostin mediates vascular smooth muscle cell migration through the integrins ανβ3 and ανβ5 and focal adhesion kinase (FAK) pathway

Department of Neurosurgery, Louisiana State University Health Sciences Center, 1501 Kings Highway, Shreveport, LA, United States.
Atherosclerosis (Impact Factor: 3.97). 02/2010; 208(2):358-65. DOI: 10.1016/j.atherosclerosis.2009.07.046
Source: PubMed

ABSTRACT Smooth muscle cell (SMC) migration involves interactions of integrin receptors with extracellular matrix (ECM) and is an important process of neointimal formation in atherosclerosis and restenosis after vascular interventions. Previous studies have shown that periostin (PN), a novel ECM protein, is upregulated in rat carotid artery after balloon injury, and growth factor-stimulated expression of PN promotes SMC migration in vitro. Here, we address the mechanism by which PN-integrin interaction mediates SMC migration in vitro. Aortic SMCs isolated from PN null mice exhibited a significantly reduced ability to migrate and proliferate in vitro. Endogenous PN protein was absent and very low in the culture medium from the primary cultures of PN-/- and wildtype SMCs, respectively. In both types of SMCs, adenovirus-mediated overexpression of HA-tagged PN to a similar extent, which induced a robust cell migration concomitantly with an increase in beta3-integrin expression and phosphorylation of FAK (Tyr397). Furthermore, in cultured human SMCs, specific integrin blocking antibodies showed that interactions of PN-alphanubeta3 and PN-alphanubeta5, but not PN-beta1 integrins, are required for SMC migration. Inhibition of FAK signaling by overexpression of an endogenous FAK inhibitor termed FRNK (FAK-related nonkinase) significantly attenuated FAK (Tyr397) phosphorylation and the SMC migration induced by PN. These results reveal a mechanism whereby PN mediates vascular SMC migration through an interaction with alphaV-integrins (mainly alphanubeta3) and subsequent activation of FAK pathway.

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Available from: Daniel Neil Granger, Jul 19, 2015
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    • "In colon and ovarian cancers, periostin exerts pro-metastatic effects through α v β 3 and/or α v β 5 receptors by increasing cell motility and survival both in vivo and in vitro (Gillan et al., 2002; Bao et al., 2004; Tai et al., 2005). As a cell adhesion molecule, periostin can facilitate invasion in tumor microenvironment and contribute to a novel tumorinvasive signature in esophageal cancer, and the induction of periostin is dependent on EGFR signaling and mutant p53 (Michaylira et al., 2010). The periostin mRNA level is very high in pancreatic cancer. "
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    ABSTRACT: The behavior and fate of cells in tissues largely rely upon their cross-talk with the tissue microenvironment including neighboring cells, the extracellular matrix (ECM), and soluble cues from the local and systemic environments. Dysregulation of tissue microenvironment can drive various inflammatory diseases and tumors. The ECM is a crucial component of tissue microenvironment. ECM proteins can not only modulate tissue microenvironment but also regulate the behavior of surrounding cells and the homeostasis of tissues. As a nonstructural ECM protein, periostin is generally present at low levels in most adult tissues; however, periostin is often highly expressed at sites of injury or inflammation and in tumors within adult organisms. Current evidence demonstrates that periostin actively contributes to tissue injury, inflammation, fibrosis and tumor progression. Here, we summarize the roles of periostin in inflammatory and tumor microenvironments.
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    • "Loss of periostin results in altered wound-closure kinetics Periostin is upregulated following acute injury to skin in wild-type mice (Jackson-Boeters et al., 2009; Lindner et al., 2005; Zhou et al., 2010). To investigate the contribution of periostin to the dermal wound repair process, full-thickness excisional wounds were created in Postn 2/2 mice and their sex-and age-matched Postn +/+ littermates. "
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    ABSTRACT: The matricellular protein periostin is expressed in the skin. Although periostin has been hypothesized to contribute to dermal homeostasis and repair, this has not been directly tested. To assess the contribution of periostin to dermal healing, 6 mm full-thickness excisional wounds were created in the skin of periostin-knockout and wild-type, sex-matched control mice. In wild-type mice, periostin was potently induced 5–7 days after wounding. In the absence of periostin, day 7 wounds showed a significant reduction in myofibroblasts, as visualized by expression of a-smooth muscle actin (a-SMA) within the granulation tissue. Delivery of recombinant human periostin by electrospun collagen scaffolds restored a-SMA expression. Isolated wild-type and knockout dermal fibroblasts did not differ in in vitro assays of adhesion or migration; however, in 3D culture, periostin-knockout fibroblasts showed a significantly reduced ability to contract a collagen matrix, and adopted a dendritic phenotype. Recombinant periostin restored the defects in cell morphology and matrix contraction displayed by periostin-deficient fibroblasts in a manner that was sensitive to a neutralizing anti-b1-integrin and to the FAK and Src inhibitor PP2. We propose that periostin promotes wound contraction by facilitating myofibroblast differentiation and contraction. Introduction Periostin is a secreted 90 kDa, disulfide-linked protein, which has structural similarity with the insect adhesion protein, fasciclin-1 (Takeshita et al., 1993). During development, periostin is expressed by cardiac fibroblasts in the embryonic heart (Kruzynska-Frejtag et al., 2001), where it facilitates organization of the extracellular matrix (ECM) (Snider et al., 2009) and differentiation of mesenchymal cushion progenitor cells into contractile myofibroblasts (Conway and Molkentin, 2008). Recent research has now highlighted increased periostin expression in various disease states, including myocardial infarction (Iekushi et al., 2007; Oka et al., 2007; Shimazaki et al., 2008) and cancer (Baril et al., 2007; Erkan et al., 2007; Gillan et al., 2002). In particular, periostin is heavily implicated in fibrosis including bone marrow (Oku et al., 2008), subepithelial fibrosis of bronchial asthma (Takayama et al., 2006), fibrous dysplasia (Kashima et al., 2009), and keloid and hypertrophic scarring of the skin (Naitoh et al., 2005; Wang et al., 2007a). Additionally, induction of periostin expression has been described following acute injury to numerous tissues (Goetsch et al., 2003; Li et al., 2006; Lindner et al., 2005; Nakazawa et al., 2004), including skin (Jackson-Boeters et al., 2009; Lindner et al., 2005; Zhou et al., 2010), where expression peaks at 7–8 days and returns to basal levels by 4 weeks. Our previous reports on skin repair show that periostin expression is absent during inflammation, but instead corresponds with the proliferative and remodeling phases of repair (Jackson-Boeters et al., 2009; Zhou et al., 2010), suggesting a role for periostin during these later phases. Fibroblasts are central to the proliferative and remodeling phases of skin (Ross, 1968). Dysregulation of fibroblast function in skin can result in inadequate repair (Blumbach et al., 2010; Shimazaki et al., 2008) or excessive matrix production (fibrosis) (Babu et al., 1992; Leask, 2010). Activated fibroblasts, or myofibroblasts, are fibroblasts that have differentiated into a contractile phenotype, characterized by the expression of a-smooth muscle actin (a-SMA) (Gabbiani et al., 1972). During wound repair, they serve to expedite wound closure by drawing the edges of the wound together through generation of contractile forces (Gabbiani et al., 1972; Gabbiani et al., 1971; Majno et al., 1971), which are transmitted to the ECM through integrin-containing adhesion complexes known as focal adhesions (Burridge and Chrzanowska-Wodnicka, 1996). Numerous studies have implicated periostin with expression of a-SMA
    Journal of Cell Science 07/2011; 125:121-132. · 5.33 Impact Factor
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    ABSTRACT: Differentiation of fibroblasts to myofibroblasts and collagen fibrillogenesis are two processes essential for normal cutaneous development and repair, but their misregulation also underlies skin-associated fibrosis. Periostin is a matricellular protein normally expressed in adult skin, but its role in skin organogenesis, incisional wound healing and skin pathology has yet to be investigated in any depth. Using C57/BL6 mouse skin as model, we first investigated periostin protein and mRNA spatiotemporal expression and distribution during development and after incisional wounding. Secondarily we assessed whether periostin is expressed in human skin pathologies, including keloid and hypertrophic scars, psoriasis and atopic dermatitis. During development, periostin is expressed in the dermis, basement membrane and hair follicles from embryonic through neonatal stages and in the dermis and hair follicle only in adult. In situ hybridization demonstrated that dermal fibroblasts and basal keratinocytes express periostin mRNA. After incisional wounding, periostin becomes re-expressed in the basement membrane within the dermal-epidermal junction at the wound edge re-establishing the embryonic deposition pattern present in the adult. Analysis of periostin expression in human pathologies demonstrated that it is over-expressed in keloid and hypertrophic scars, atopic dermatitis, but is largely absent from sites of inflammation and inflammatory conditions such as psoriasis. Furthermore, in vitro we demonstrated that periostin is a transforming growth factor beta 1 inducible gene in human dermal fibroblasts. We conclude that periostin is an important ECM component during development, in wound healing and is strongly associated with pathological skin remodeling.Summary: Periostin is a fibrogenic protein that mediates fibroblast differentiation and extracellular matrix synthesis. Here, we show that periostin is dynamically and temporally expressed during skin development, is induced by TGF-beta1 in vitro and is significantly upregulated during wound repair as well as cutaneous pathologies.
    Journal of Cell Communication and Signaling 06/2010; 4(2):99-107. DOI:10.1007/s12079-010-0090-2
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