Article

Periostin is required for maturation and extracellular matrix stabilization of noncardiomyocyte lineages of the heart

Cardiovascular Development Group, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, USA.
Circulation Research (Impact Factor: 11.09). 05/2008; 102(7):752-60. DOI: 10.1161/CIRCRESAHA.107.159517
Source: PubMed

ABSTRACT The secreted periostin protein, which marks mesenchymal cells in endocardial cushions following epithelial-mesenchymal transformation and in mature valves following remodeling, is a putative valvulogenesis target molecule. Indeed, periostin is expressed throughout cardiovascular morphogenesis and in all 4 adult mice valves (annulus and leaflets). Additionally, periostin is expressed throughout the fibrous cardiac skeleton and endocardial cushions in the developing heart but is absent from both normal and/or pathological mouse cardiomyocytes. Periostin (peri(lacZ)) knockout mice exhibit viable valve disease, with neonatal lethality in a minority and latent disease with leaflet abnormalities in the viable majority. Surviving peri(lacZ)-null leaflets are truncated, contain ectopic cardiomyocytes and smooth muscle, misexpress the cartilage proteoglycan aggrecan, demonstrate disorganized matrix stratification, and exhibit reduced transforming growth factor-beta signaling. Neonatal peri(lacZ) nulls that die (14%) display additional defects, including leaflet discontinuities, delamination defects, and deposition of acellular extracellular matrix. Assessment of collagen production, 3D lattice formation ability, and transforming growth factor-beta responsiveness indicate periostin-deficient fibroblasts are unable to support normal valvular remodeling and establishment of a mature cardiac skeleton. Furthermore, pediatric stenotic bicuspid aortic valves that have lost normal extracellular matrix trilaminar stratification have greatly reduced periostin. This suggests that loss of periostin results in inappropriate differentiation of mesenchymal cushion cells and valvular abnormalities via a transforming growth factor-beta-dependent pathway during establishment of the mature heart. Thus, peri(lacZ) knockouts provide a new model of viable latent valve disease.

Download full-text

Full-text

Available from: Anthony B Firulli, Jun 29, 2015
0 Followers
 · 
139 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The matricellular protein periostin is strongly expressed in collagen-rich connective tissues such as periodontal ligaments, skeletal muscle, adipose tissue, tendons, skin, and bone. It is prominent in tumorigenesis, angiogenesis, and cardiac repair. It is localized in the periosteum and periodontal ligament, where it is seen in the cytoplasmic extensions of the periodontal ligament fibroblasts. It plays a key role in morphogenesis, postnatal development, and maintenance of the tooth and related structures. It mediates and augments collagen fibrillogenesis, cell migration, adhesion, response to mechanical stress, and wound healing. It has been shown to be an integral regulator of periodontal disease pathogenesis and repair. This review focuses on the various functional aspects of periostin in dental connective tissue development and maintenance. J. Cell. Physiol. © 2013 Wiley Periodicals, Inc.
    Journal of Cellular Physiology 05/2013; 229(1). DOI:10.1002/jcp.24407 · 3.87 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Bronchopulmonary dysplasia (BPD) is a chronic lung disease affecting premature infants with long term effect on lung function into adulthood. Multiple factors are involved in the development of BPD. This review will summarize the different mechanisms leading to this disease and highlight recent bench and clinical research targeted at understanding the role of the mesenchyme (both its cellular and extracellular components) in the pathogenesis of BPD.
    Journal of Cell Communication and Signaling 01/2013; 7(2). DOI:10.1007/s12079-013-0190-x
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The majority of children with congenital heart disease now live into adulthood due to the remarkable surgical and medical advances that have taken place over the past half century. Because of this, adults now represent the largest age group with adult cardiovascular diseases. It includes patients with heart diseases that were not detected or not treated during childhood, those whose defects were surgically corrected but now need revision due to maladaptive responses to the procedure, those with exercise problems and those with age-related degenerative diseases. Because adult cardiovascular diseases in this population are relatively new, they are not well understood. It is therefore necessary to understand the molecular and physiological pathways involved if we are to improve treatments. Since there is a developmental basis to adult cardiovascular disease, transforming growth factor beta (TGFβ) signaling pathways that are essential for proper cardiovascular development may also play critical roles in the homeostatic, repair and stress response processes involved in adult cardiovascular diseases. Consequently, we have chosen to summarize the current information on a subset of TGFβ ligand and receptor genes and related effector genes that, when dysregulated, are known to lead to cardiovascular diseases and adult cardiovascular deficiencies and/or pathologies. A better understanding of the TGFβ signaling network in cardiovascular disease and repair will impact genetic and physiologic investigations of cardiovascular diseases in elderly patients and lead to an improvement in clinical interventions.
    Cell and Tissue Research 09/2011; 347(1):203-23. DOI:10.1007/s00441-011-1241-3 · 3.33 Impact Factor