Alternative titles; symbols
HGNC Approved Gene Symbol: POSTN
Cytogenetic location: 13q13.3 Genomic coordinates (GRCh38) : 13:37,562,585-37,598,768 (from NCBI)
Takeshita et al. (1993) cloned mouse Postn, which they designated Osf2. By screening human placenta and osteosarcoma cDNA libraries with mouse Postn as probe, they cloned 2 variants of human POSTN. One variant encodes a deduced 779-amino acid protein with an apparent molecular mass of 87.0 kD, and the other encodes a deduced 836-amino acid protein with an apparent molecular mass of 93.3 kD. POSTN contains a typical signal sequence, followed by a cysteine-rich domain, a 4-fold repeat structure of about 150 amino acids, and a C-terminal domain. Mouse and human POSTN share 89.2% amino acid identity overall and 90.1% identity in their mature forms. Northern blot analysis of a mouse osteoblastic cell line detected a 3.4-kb Postn transcript. RNA dot blot analysis detected expression of Postn in primary mouse osteoblasts and in lung, but not in any other tissues examined.
Gillan et al. (2002) identified a periostin (PN) EST clone encoding a deduced 782-amino acid protein. RNA dot blot analysis detected PN expression in a wide range of normal adult tissues, including aorta, stomach, lower gastrointestinal tract, placenta, uterus, and breast. PN was expressed at variable levels in all fetal tissues examined. Western blot analysis detected strong periostin staining in fetal calf serum, but not in newborn calf serum. Gillan et al. (2002) found that PN was secreted by cultures derived from epithelial ovarian cancer, but not from normal ovarian epithelial cells. They identified multiple protein bands of about 90 kD, as well as a band of about 170 kD, which may represent a covalently linked multimer. PN was present in 20 of 21 ascites from ovarian cancer patients.
Gillan et al. (2002) found that purified recombinant PN supported adhesion of ovarian epithelial cells. Adhesion was inhibited by antibodies against alpha-V (ITGAV; 193210)/beta-3 (ITGB3; 173470) or alpha-V/beta-5 (ITGB5; 147561) integrins, but not by antibodies against beta-1 integrin (ITGB1; 135630). Furthermore, alpha-V/beta-3 integrin, but not beta-1 integrin, colocalized to the focal adhesion plaques formed on PN. Cells plated on PN formed fewer stress fibers and were more motile compared with those plated on fibronectin (135600). Gillan et al. (2002) concluded that PN functions as a ligand for alpha-V/beta-3 and alpha-V/beta-5 integrins to support adhesion and migration of ovarian epithelial cells.
Shao et al. (2004) found that periostin was overexpressed by the majority of human primary breast cancers examined. Transfected tumor cell lines overexpressing periostin showed accelerated growth and angiogenesis as xenografts in immunocompromised animals. Periostin-mediated angiogenesis was derived in part from upregulation of vascular endothelial growth factor receptor (KDR; 191306) by endothelial cells through an alpha-V/beta-3 integrin-focal adhesion kinase (600758)-mediated signaling pathway.
Using gene expression microarrays, Woodruff et al. (2007) found that CLCA1 (603906), POSTN, and SERPINB2 (PAI2; 173390) were upregulated in airway epithelial cells of individuals with asthma (see 600807), but not smokers. Corticosteroid treatment downregulated expression of these 3 genes and upregulated expression of FKBP51 (602623). High baseline expression of CLCA1, POSTN, and SERPINB2 was associated with a good clinical response to corticosteroids, whereas high expression of FKBP51 was associated with a poor response. Treatment of airway epithelial cells with IL13 resulted in increased expression of CLCA1, POSTN, and SERPINB2, an effect that could be suppressed by corticosteroids.
Kuhn et al. (2007) showed that extracellular periostin induced reentry of differentiated mammalian cardiomyocytes into the cell cycle. Periostin stimulated mononucleated cardiomyocytes to go through the full mitotic cell cycle. Periostin activated alpha-V, beta-1, beta-3, and beta-5 integrins located in the cardiomyocyte cell membrane. Activation of phosphatidylinositol-3-OH kinase (see 171833) was required for periostin-induced reentry of cardiomyocytes into the cell cycle and was sufficient for cell cycle reentry in the absence of periostin. After myocardial infarction, periostin-induced cardiomyocyte cell cycle reentry and mitosis were associated with improved ventricular remodeling and myocardial function, reduced fibrosis and infarct size, and increase angiogenesis.
Using immunohistochemical analysis, Snider et al. (2008) showed that periostin was expressed in pediatric aortic valves in a trilaminar pattern, with increased expression in fibrosa and spongiosa relative to ventricularis. Stenotic pediatric bicuspid valves that had lost normal trilaminar stratification of the extracellular matrix showed greatly reduced periostin expression. In mice, periostin was expressed throughout cardiac development in the fibrous cardiac skeleton and endocardial cushions, but it was absent from cardiomyocytes. Periostin was detected in all 4 adult mouse valves examined.
Malanchi et al. (2012) demonstrated that a small population of cancer stem cells is critical for metastatic colonization, i.e., the initial expansion of cancer cells at the secondary site, and that stromal niche signals are crucial to this expansion process. The authors found that periostin, a component of the extracellular matrix, is expressed by fibroblasts in the normal tissue and in the stroma of the primary tumor. Infiltrating tumor cells need to induce stromal POSTN expression in the secondary target organ (in this case the lung) to initiate colonization. POSTN is required to allow cancer stem cell maintenance, and blocking its function prevents metastasis. POSTN recruits Wnt ligands and thereby increases Wnt signaling in cancer stem cells. Malanchi et al. (2012) suggested that the education of stromal cells by infiltrating tumor cells is an important step in metastatic colonization and that preventing de novo niche formation may be a novel strategy for the treatment of metastatic disease.
The International Radiation Hybrid Mapping Consortium mapped the POSTN gene to chromosome 13 (STS-H12747).
Snider et al. (2008) found that periostin-null mice exhibited variable cardiac valve disease, with neonatal lethality in 14%. Periostin-null animals that survived showed truncated leaflets with ectopic cardiomyocytes and smooth muscle cells, misexpression of the cartilage proteoglycan aggrecan (ACAN; 155760), disorganized matrix stratification, and reduced Tgf-beta (TGFB1; 190180) signaling. Those that died also showed leaflet discontinuities, delamination defects, and deposition of acellular extracellular matrix. Periostin-deficient fibroblasts were unable to support normal valve remodeling or establish a mature cardiac skeleton. Snider et al. (2008) concluded that periostin is required for TGF-beta-dependent development of noncardiomyocyte lineages in the heart.
Gillan, L., Matei, D., Fishman, D. A., Gerbin, C. S., Karlan, B. Y., Chang, D. D. Periostin secreted by epithelial ovarian carcinoma is a ligand for alpha-V-beta-3 and alpha-V-beta-5 integrins and promotes cell motility. Cancer Res. 62: 5358-5364, 2002. [PubMed: 12235007]
Kuhn, B., del Monte, F., Hajjar, R. J., Chang, Y.-S., Lebeche, D., Arab, S., Keating, M. T. Periostin induces proliferation of differentiated cardiomyocytes and promotes cardiac repair. Nature Med. 13: 962-969, 2007. [PubMed: 17632525] [Full Text: https://doi.org/10.1038/nm1619]
Malanchi, I., Santamaria-Martinez, A., Susanto, E., Peng, H., Lehr, H.-A., Delaloye, J.-F., Huelsken, J. Interactions between cancer stem cells and their niche govern metastatic colonization. Nature 481: 85-89, 2012.
Shao, R., Bao, S., Bai, X., Blanchette, C., Anderson, R. M., Dang, T., Gishizky, M. L., Marks, J. R., Wang, X.-F. Acquired expression of periostin by human breast cancers promotes tumor angiogenesis through up-regulation of vascular endothelial growth factor receptor 2 expression. Molec. Cell. Biol. 24: 3992-4003, 2004. [PubMed: 15082792] [Full Text: https://doi.org/10.1128/MCB.24.9.3992-4003.2004]
Snider, P., Hinton, R. B., Moreno-Rodriguez, R. A., Wang, J., Rogers, R., Lindsley, A., Li, F., Ingram, D. A., Menick, D., Field, L., Firulli, A. B., Molkentin, J. D., Markwald, R., Conway, S. J. Periostin is required for maturation and extracellular matrix stabilization of noncardiomyocyte lineages of the heart. Circ. Res. 102: 752-760, 2008. [PubMed: 18296617] [Full Text: https://doi.org/10.1161/CIRCRESAHA.107.159517]
Takeshita, S., Kikuno, R., Tezuka, K., Amann, E. Osteoblast-specific factor 2: cloning of a putative bone adhesion protein with homology with the insect protein fasciclin 1. Biochem. J. 294: 271-278, 1993. [PubMed: 8363580] [Full Text: https://doi.org/10.1042/bj2940271]
Woodruff, P. G., Boushey, H. A., Dolganov, G. M., Barker, C. S., Yang, Y. H., Donnelly, S., Ellwanger, A., Sidhu, S. S., Dao-Pick, T. P., Pantoja, C., Erle, D. J., Yamamoto, K. R., Fahy, J. V. Genome-wide profiling identifies epithelial cell genes associated with asthma and with treatment response to corticosteroids. Proc. Nat. Acad. Sci. 104: 15858-15863, 2007. [PubMed: 17898169] [Full Text: https://doi.org/10.1073/pnas.0707413104]