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: 11.02). 05/2008; 102(7):752-60. DOI: 10.1161/CIRCRESAHA.107.159517
Source: PubMed


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.

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Available from: Anthony B Firulli, Oct 10, 2015
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    • "Brodarac, Impaired tooth development in periostin deficient mice, PhD thesis, University of Hamburg, 2006) and causes secondary defects such as malnutrition and dwarfism (Kii et al., 2006; Rios et al., 2005). More recent studies involving different challenging strategies have revealed subtle defects in skin, tendons, heart valves, and changes in regeneration dynamics following myocardial infarction (Norris et al., 2008, 2007; Oka et al., 2007; Shimazaki and Kudo, 2008; Snider et al., 2008). Interestingly, subtle phenotypes during normal development and impairment of tissue remodelling and repair are hallmarks of mice carrying targeted mutations in other matricellular proteins (Bornstein and Sage, 2002). "
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    ABSTRACT: Neuregulin ligands and their erbB receptors are important for the development of Schwann cells (SCs), the glial cells of the peripheral nervous system (PNS). ErbB3 deficiency is characterized by a complete loss of SCs along axons of the peripheral nerves, impaired fasciculation and neuronal cell death. We performed comparative gene expression analysis of dorsal root ganglia (DRG) explant cultures from erbB3 deficient and wild type mice to identify genes that are involved in SC development and migration. The extracellular matrix (ECM) gene periostin was found to exhibit the most prominent down regulation in erbB3 deficient DRG. Expression analysis revealed that the periostin expressing cell population in the PNS corresponds to SC precursors and SCs and is particularly high in migratory SCs. Furthermore; stimulation of SCs with neuregulin‑1 (NRG1) or transforming growth factor β (TGFβ) resulted in an upregulation of periostin expression. Interestingly, DRG explant cultures of periostin deficient mice revealed a significant reduction of the number of migrating SCs. These data demonstrate that the expression of periostin is stimulated by erbB ligand NRG1 and influences the migration of SC precursors. © 2015. Published by The Company of Biologists Ltd.
    Journal of Cell Science 07/2015; 128(17). DOI:10.1242/jcs.174177 · 5.43 Impact Factor
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    • "Activation of myocardial fibroblasts through both stretch-related signaling and neuron-endocrine effectors led to the secretion of various ECM proteins. These proteins conducted molecular signals, regulated cell kinetics and finally altered the structure of extra-cellular matrix [3], [4]. "
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    ABSTRACT: Periostin was proved to play an important role in extra-cellular matrix remodeling after acute myocardial infarction (AMI). Myocardial periostin was markedly up-regulated after AMI and participated in the maladaptive process of cardiac remodeling. However, few researches focused on the circulating periostin and its significance. This study aims to investigate the association of serum periostin level with cardiac function and short-term prognosis in AMI patients. We totally recruited 50 patients diagnosed as ST-elevation myocardial infarction. Blood samples were taken within 12 hours after the onset of AMI before emergency coronary revascularization procedures. Serum periostin was measured using enzyme-linked immunosorbent assay. All patients received echocardiography examination within one week after hospitalization. Correlations of serum periostin with echocardiography parameters, Killip class and myocardium injury biomarkers (CK-MB/troponin T) were investigated. AMI patients were divided into two groups by serum periostin level (higher/lower periostin group) and followed up for six months. Primary endpoints included cardiovascular mortality, nonfatal stroke/transient ischemic attack, chest pain occurrence and re-hospitalization. Secondary endpoint referred to composite cardiovascular events including all the primary endpoints. Serum periostin was in negative association with left ventricular ejection fraction (LVEF) (r = -0.472, *p<0.01) and left atrium diameter (LAD) (r = -0.328, *p<0.05). Positive correlation was found between serum periostin level and Killip class (r = 0.395, *p<0.01). There was no association between serum periostin and CK-MB or troponin T (p>0.05). After six months follow up, patients in higher periostin group showed increased composite cardiovascular events (*p<0.05). Patients showed no significant difference in primary endpoints between the two groups. Serum periostin was in negative correlation with LVEF and LAD, in positive association with Killip class and higher serum periostin level may be predictive for worse short-term disease prognosis indicated as more composite cardiovascular events six months post AMI.
    PLoS ONE 02/2014; 9(2):e88755. DOI:10.1371/journal.pone.0088755 · 3.23 Impact Factor
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    • "This variance may be due to the variety of the etiologies of the patients in this study. Periostin may be an indicator of ECM synthesis because it is co-expressed intracellularly with collagen I in the cytoplasmic endoplasmic reticulum/Golgi [19]. Our data showed there existed an increased mRNA expression of periostin in failing heart tissues and protein expression was detected in different parts of the hearts, especially in left ventricles. "
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    ABSTRACT: Periostin, a matricellular protein, plays an important role in cardiac development and remodeling. Its expression profile and the association with myocardial fibrosis have not been investigated in human failing hearts. This work aimed to explore the behavior and pathologic significance of periostin in signifying collagen fibrogenesis in human hearts from patients with end-stage heart failure. Tissues were collected from heart transplant recipients and the control hearts were from unmatched donors. Periostin mRNA and protein were detected using quantitative real-time polymerase chain reaction and Western blotting. Immunohistochemistry staining was employed to directly detect the protein level and distribution of periostin in heart tissues. The extent of myocardial fibrosis was expressed by the percentage of Masson's trichrome staining. Gelatin zymography was used to detect the activities of matrix metalloproteinase (MMP)2 and MMP9. A low level of periostin mRNA expression was found in control hearts while not detectable at the protein level. Periostin mRNA was increased significantly in failing myocardium compared to that of controls. Periostin was distributed extensively in left ventricle and interventricular septum of the failing hearts. Correlation analysis showed periostin protein expression was positively associated with myocardial fibrosis as well as left ventricular diastolic dimension. The distribution and extent of periostin was consistent with that of myocardial fibrosis. MMP2 activity has an obvious increase about fourfold in heart tissues from HF patients. But there is no quantitative association with the expression of periostin. Periostin, the distribution and expression of which were consistent with the extent of myocardial fibrosis, might be a potential biomarker of cardiac remodeling in heart failure patients.
    Journal of Cardiology 11/2013; 63(5). DOI:10.1016/j.jjcc.2013.09.013 · 2.78 Impact Factor
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