1. Gene Aliases

Periostin, OSF-2, PN, Periostin, Osteoblast Specific Factor, OSF2, Osteoblast Specific Factor 2 (Fasciclin I-Like), Periodontal Ligament-Specific Periostin, Osteoblast Specific Factor 2, Osteoblast-Specific Factor 2, PERIOSTIN, PDLPOSTN

[https://www.genecards.org/cgi-bin/carddisp.pl?gene=POSTN]

2. Association with Toxicity and/or Disease at a Transcriptional Level

3. Summary of Protein Family and Structure

4. Proteins Known to Interact with Gene Product

Interactions with experimental support

Interactions with text mining support

5. Links to Gene Databases

6. GO Terms, MSigDB Signatures, Pathways Containing Gene with Descriptions of Gene Sets

Pathways:

Amplification and expansion of oncogenic pathways as metastatic traits: The majority of cancer cells released from tumors die off, so cancer biologists are trying to figure out exactly what gives certain cells the ability to colonize other distant organs. Specific genes and mediators of metastasis have been identified, but it remains mostly unknown how cancer cells acquire these traits. Metastatic traits acquired by a quantitative gain in pathway output: These pathways demonstrate metastatic traits acquired by a quantitative gain in pathway output. The PI3K-Akt signaling pathway, which is augmented by VCAM-1 and SRC, leads to increased cell survival, a significant metastatic trait. Similarly, TCF augments the output of the NOTCH and, along with periostin, Wnt signaling pathways. As the signaling of these pathways increases, the metastatic and oncogenic potential of the cell also increase. Metastatic traits acquired by a qualitative expansion of pathway output: This pathway demonstrates metastatic traits acquired by a qualitative expansion of pathway output. Loss of the von Hippel-Lindau tumor suppressor (VHL) in renal cell carcinoma leads to increased activation of hypoxia-inducible transcription factors (HIFs). Histone H3K27 and CYTIP give the VHL-HIF pathway access to new target genes. Each of these new target genes, in this case CXCR4, VEGFA, and CYTIP, lead to an increase in a metastatic trait. Here, the level of metastatic fitness is not linearly proportional to pathway activity; rather, the pathway activates an additional set of factors that affect metastatic fitness. [https://www.wikipathways.org/pathways/WP3678.html].

Hypothesized pathways in pathogenesis of cardiovascular disease: The pathways hypothesized to be involved in cardiovascular diseases begin with LTBPs and Fibrillins activating a TGFBR complex. The complex can begin the canonical TGFB pathway involving SMAD proteins that target gene expression for proteins involved in endocardial and epicardial EMT, neural crest migration, ECM remodeling, cell differentiation, development and maintenance of cardiovascular structure and function. The non-canonical TGFB pathway involves the calcium-calneurin signaling pathway that also affects the previously mentioned functions. the TGFBR complex also activates SHCA and Tak1 which promote the function of a complex (ERK1/2, JNK1, and p38) to regulate the previously mentioned cell functions and influence the development of cardiovascular diseases. These diseases are additionally influenced by a signalling pathway involving the activation of TGFB ligands, receptors, activators, and effectors by ANG2/AT1/2R complex. This pathway is based on figure 1 from Doetschman et al. [https://www.wikipathways.org/pathways/WP3668.html].

GO terms:

bone regeneration [The regrowth of bone following its loss or destruction. GO:1990523]

cell adhesion [The attachment of a cell, either to another cell or to an underlying substrate such as the extracellular matrix, via cell adhesion molecules. GO:0007155]

cellular response to fibroblast growth factor stimulus [Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an fibroblast growth factor stimulus. GO:0044344]

cellular response to transforming growth factor beta stimulus [Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a transforming growth factor beta stimulus. GO:0071560]

cellular response to tumor necrosis factor [Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a tumor necrosis factor stimulus. GO:0071356]

cellular response to vitamin K [Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a vitamin K stimulus. GO:0071307]

extracellular matrix organization [A process that is carried out at the cellular level which results in the assembly, arrangement of constituent parts, or disassembly of an extracellular matrix. GO:0030198]

negative regulation of cell-matrix adhesion [Any process that stops, prevents, or reduces the rate or extent of cell adhesion to the extracellular matrix. GO:0001953]

negative regulation of substrate adhesion-dependent cell spreading [Any process that stops, prevents or reduces the frequency, rate or extent of substrate adhesion-dependent cell spreading. GO:1900025]

neuron projection extension [Long distance growth of a single neuron projection involved in cellular development. A neuron projection is a prolongation or process extending from a nerve cell, e.g. an axon or dendrite. GO:1990138]

positive regulation of chemokine (C-X-C motif) ligand 2 production [Any process that activates or increases the frequency, rate or extent of chemokine (C-X-C motif) ligand 2 production. GO:2000343]

positive regulation of smooth muscle cell migration [Any process that activates, maintains or increases the frequency, rate or extent of smooth muscle cell migration. GO:0014911]

regulation of Notch signaling pathway [Any process that modulates the frequency, rate or extent of the Notch signaling pathway. GO:0008593]

regulation of systemic arterial blood pressure [The process that modulates the force with which blood travels through the systemic arterial circulatory system. The process is controlled by a balance of processes that increase pressure and decrease pressure. GO:0003073]

response to estradiol [Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of stimulus by estradiol, a C18 steroid hormone hydroxylated at C3 and C17 that acts as a potent estrogen. GO:0032355]

response to hypoxia [Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a stimulus indicating lowered oxygen tension. Hypoxia, defined as a decline in O2 levels below normoxic levels of 20.8 - 20.95%, results in metabolic adaptation at both the cellular and organismal level.|Note that this term should not be confused with 'response to anoxia ; GO:0034059'. Note that in laboratory studies, hypoxia is typically studied at O2 concentrations ranging from 0.1 - 5%. GO:0001666]

response to mechanical stimulus [Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a mechanical stimulus. GO:0009612]

response to muscle activity [Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a muscle activity stimulus. GO:0014850]

tissue development [The process whose specific outcome is the progression of a tissue over time, from its formation to the mature structure. GO:0009888]

MSigDB Signatures:

WP_HYPOTHESIZED_PATHWAYS_IN_PATHOGENESIS_OF_CARDIOVASCULAR_DISEASE: Hypothesized pathways in pathogenesis of cardiovascular disease [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/WP_HYPOTHESIZED_PATHWAYS_IN_PATHOGENESIS_OF_CARDIOVASCULAR_DISEASE.html]

7. Gene Descriptions

NCBI Gene Summary: This gene encodes a secreted extracellular matrix protein that functions in tissue development and regeneration, including wound healing, and ventricular remodeling following myocardial infarction. The encoded protein binds to integrins to support adhesion and migration of epithelial cells. This protein plays a role in cancer stem cell maintenance and metastasis. Mice lacking this gene exhibit cardiac valve disease, and skeletal and dental defects. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Sep 2015]

GeneCards Summary: POSTN (Periostin) is a Protein Coding gene. Diseases associated with POSTN include Myocardial Infarction and T2-High Asthma. Among its related pathways are Amplification and expansion of oncogenic pathways as metastatic traits and Hypothesized pathways in pathogenesis of cardiovascular disease. Gene Ontology (GO) annotations related to this gene include heparin binding and cell adhesion molecule binding. An important paralog of this gene is TGFBI.

UniProtKB/Swiss-Prot Summary: Induces cell attachment and spreading and plays a role in cell adhesion [PMID: 12235007]. Enhances incorporation of BMP1 in the fibronectin matrix of connective tissues, and subsequent proteolytic activation of lysyl oxidase LOX.

8. Cellular Location of Gene Product

Distinct expression in extracellular matrix. Mainly localized to the Golgi apparatus. Predicted location: Secreted [https://www.proteinatlas.org/ENSG00000133110/subcellular]

9. Mechanistic Information

Summary

The Postn gene, encoding periostin, is dysregulated in heart-related diseases and toxicities as a direct response to tissue damage and the subsequent need for repair and remodeling [CS: 8]. In the context of myocardial infarction or chronic heart failure, when the heart undergoes significant stress and damage leading to tissue fibrosis and organ dysfunction, periostin plays a crucial role by promoting cell adhesion, spreading, and the incorporation of BMP1 into the fibronectin matrix, thus facilitating the repair and restructuring of damaged cardiac tissue [CS: 7].

Specifically, in conditions like acute myocardial infarction or cardiomyopathies, Postn expression is significantly increased [CS: 9]. This upregulation aids the heart's response to injury by enhancing extracellular matrix (ECM) degradation and fibrosis, key processes in tissue remodeling [CS: 8]. By binding to integrins and supporting epithelial cell adhesion and migration, periostin helps in forming a stable and supportive tissue structure post-injury [CS: 9]. This function counteracts the initial damage by reinforcing the structural integrity of the heart, thereby aiding its recovery and sustaining its function despite the injury [CS: 8].

10. Upstream Regulators

11. Tissues/Cell Type Where Genes are Overexpressed

Tissue type enchanced: skin, stomach (tissue enhanced) [https://www.proteinatlas.org/ENSG00000133110/tissue]

Cell type enchanced: basal keratinocytes, breast myoepithelial cells, endothelial cells, fibroblasts, smooth muscle cells (group enriched) [https://www.proteinatlas.org/ENSG00000133110/single+cell+type]

12. Role of Gene in Other Tissues

13. Chemicals Known to Elicit Transcriptional Response of Biomarker in Tissue of Interest

Compounds that increase expression of the gene:

14. DisGeNet Biomarker Associations to Disease in Organ of Interest