Browsing by Subject "Postn"

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    Periostin as a Multifunctional Modulator of the Wound Healing Response
    (Springer, 2016-09) Walker, John T.; McLeod, Karrington; Kim, Shawna; Conway, Simon J.; Hamilton, Douglas W.; Pediatrics, School of Medicine
    During tissue healing, dynamic and temporal alterations occur in the structure and composition of the extracellular matrix (ECM) that are required for effective repair to occur. Matricellular proteins (MPs) are a group of diverse non-structural ECM components, which bind cell surface receptors mediating interactions between the cell and its microenviroment, effectively regulating adhesion, migration, proliferation, signaling and cell phenotype. Periostin (Postn), a pro-fibrogenic secreted glycoprotein, was defined as a MP based on its expression pattern and regulatory roles during development, healing and in disease processes. Postn consists of a typical signal sequence, an EMI domain responsible for binding to fibronectin, four tandem fasciclin-like domains that are responsible for integrin binding and a C-terminal region where multiple splice variants originate. This review will focus specifically on the role of Postn in wound healing and remodeling, an area of intense research in the last 10 years particularly related to skin healing as well as in myocardium post infarction. Postn interacts with cells through various integrin pairs and is an essential downstream effector of TGF-β superfamily signaling. As will be discussed, across different tissues, Postn is associated with pro-fibrogenic process, specifically, the transition of fibroblasts to myofibroblasts, collagen fibrillogenesis and ECM synthesis. Although the complexity of Postn as a modulator of cell behavior in tissue healing is only beginning to be elucidated, its expression is clearly a defining event in moving wound healing through the proliferative and remodeling phases.
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    Periostin Downregulation Is an Early Marker of Inhibited Neonatal Murine Lung Alveolar Septation
    (Wiley, 2013) Ahlfeld, Shawn K.; Gao, Yong; Wang, Jian; Horgusluoglu, Emrin; Bolanis, Esther; Clapp, D. Wade; Conway, Simon J.; Pediatrics, School of Medicine
    Background: Extreme preterm birth exposes the saccular lung to multiple teratogens, which ultimately retard alveolar development. Specifically, therapeutic high level oxygen supplementation adversely affects the premature lungs and results in blunted alveolarization. Prolonged hyperoxic lung injury has previously been shown to upregulate the matricellular protein Periostin (Postn) and stimulate ectopic accumulation of alpha smooth muscle actin (αSMA) myofibroblasts. Therapies that promote lung septation are lacking largely due to a lack of reliable early biomarkers of injury. Thus, we determined if Postn expression correlated with the initial appearance of myofibroblasts in the saccular lung and was required for early alveolar development. Methods: Lung development in C57BL/6J mice following room-air (RA, 21%-O₂) or continuous hyperoxia (85%-O₂) from birth (P0) through postnatal day P14 was correlated with Postn and αSMA expression. Alveolarization in Postn knockout mice exposed to room-air, 60%-, and 85%-O₂ was also examined. Results: Postn was widely expressed in distal lung septa through P2 to P4 and peak expression coincided with accumulation of saccular myofibroblasts. Initially, 85%-O₂ prematurely downregulated Postn and αSMA expression and suppressed proliferation before the first evidence of distal lung simplification at P4. By P14, chronic 85%-O₂ resulted in secondary upregulation of Postn and αSMA in blunted septa. Myofibroblast differentiation and alveolar development was unaffected in Postn null mice and acute 85%-O₂ exposure equally inhibited septal formation in Postn null and wild-type littermates. Conclusion: Postn expression is tightly correlated with the presence of αSMA-myofibroblasts and is a novel early biomarker of acutely inhibited alveolar septation during a crucial window of lung development.