Periostin
Periostin was originally isolated as an osteoblast-specific disulfide linked 90 kDa secreted factor that shares a structural homology to the axon guidance protein fasciclin I and that functions as a cell adhesion molecule for preosteoblasts and is thought to be involved in osteoblast recruitment, attachment and spreading. Periostin expression has previously been shown to be significantly increased by both transforming growth factor beta-1(TGFbeta1) and bone morphogenetic protein (BMP)-2. Nucleotide sequence revealed four periostin transcripts that differ in the length of the C-terminal domain.
Periostin is predominantly expressed in collagen-rich fibrous connective tissues that are subjected to constant mechanical stresses including: heart valves, tendons, perichondrium, cornea, and the periodontal ligament (PDL). Periostin can regulate collagen I fibrillogenesis and thereby serves as an important mediator of the biomechanical properties of fibrous connective tissues.
Periostin and the Heart
Periostin is highly expressed in the myocardium in patients with heart failure. To identify the function of periostin in the pathophysiology of heart failure, overexpression or loss of function of the periostin gene was examined by direct transfection into the rat heart. Overexpression of the periostin gene led to cardiac hypertrophy and dysfunction. In Dahl salt-sensitive rats, inhibition of periostin gene expression resulted in a significant increase in survival rate, accompanied by an improvement of left ventricular function.
Atrial natriuretic peptide has direct antihypertrophic actions on the heart by modulating expression of genes involved in cardiac hypertrophy. Atrial natriuretic peptide-null mice demonstrated cardiac hypertrophy at baseline and an exaggerated hypertrophic response to transverse aortic constriction associated with increased expression of the extracellular matrix molecules periostin, osteopontin, collagen I and III, and thrombospondin, as well as the extracellular matrix regulatory proteins, matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-3, and pleiotrophin compared with wildtype controls.
Periostin expression was significantly increased in infarcted myocardium (P<0.05), and treatment with valsartan significantly attenuated it at 4 weeks after myocardial infarction (P<0.05), accompanied by a significant improvement in cardiac dysfunction (P<0.05).
It was demonstrated that Ang II, as well as mechanical stretch, stimulated periostin expression in both cardiac myocytes and fibroblasts, whereas valsartan significantly attenuated the increase in periostin expression. The inhibition of periostin by valsartan might especially contribute to its beneficial effects on cardiac remodeling after myocardial infarction.
Mice lacking the gene encoding periostin were more prone to ventricular rupture in the first 10 days after a myocardial infarction, but surviving mice showed less fibrosis and better ventricular performance. Periostin(-/-) mice also showed less fibrosis and hypertrophy following long-term pressure overload, suggesting an intimate relationship between periostin and the regulation of cardiac remodeling. In contrast, inducible overexpression of periostin in the heart protected mice from rupture following myocardial infarction and induced spontaneous hypertrophy with aging. With respect to a mechanism underlying these alterations, periostin(-/-) hearts showed an altered molecular program in fibroblast function. Indeed, fibroblasts isolated from periostin(- /-) hearts were less effective in adherence to cardiac myocytes and were characterized by a dramatic alteration in global gene expression (7% of all genes).
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 alphaV, beta1, beta3 and beta5 integrins located in the cardiomyocyte cell membrane. Activation of phosphatidylinositol-3-OH kinase 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 increased angiogenesis. Thus, periostin and the pathway that it regulates may provide a target for innovative strategies to treat heart failure.
Periostin and the Vasculature
Periostin mRNA is among the most strongly upregulated transcripts in rat carotid arteries after balloon injury.
Periostin and the Lung
The gene encoding periostin is an IL-4/IL-13-inducible gene in bronchial epithelial cells. Periostin secreted by lung fibroblasts in response to IL-4 and/ or IL-13 is a novel component of subepithelial fibrosis in bronchial asthma. Periostin may contribute to this process by binding to other extracellular matrix proteins and inhibiting subepithelial fibrosis in bronchial asthma.
Periostin and Fracture Healing
Periostin is a specific marker for preosteoblasts and may play an important role in periosteal callus formation during the early stage of fracture healing.
Periostin and Cancer
Brest
Undetectable in normal human breast tissues, periostin was found to be overexpressed by the vast majority of human primary breast cancers examined. Tumor cell lines engineered to overexpress periostin showed a phenotype of accelerated growth and angiogenesis as xenografts in immunocompromised animals. These findings demonstrate the presence of a novel mechanism by which tumor angiogenesis is acquired with the expression of a mesenchymespecific gene as a crucial step in late stages of tumorigenesis. Aberrant gene expression of periostin in breast cancer cells is associated to an abnormal nuclear localization of the protein. The nuclear localization of periostin in breast cancer may induce significant biological effects.
Colon
Acquired expression of periostin by colon cancer cells greatly promoted metastatic development of colon tumors. Periostin is overexpressed in more than 80% of human colon cancers examined with highest expression in metastatic tumors. Periostin expression dramatically enhanced metastatic growth of colon cancer by both preventing stress-induced apoptosis in the cancer cells and augmenting endothelial cell survival to promote angiogenesis. At the molecular level, periostin activated the Akt/PKB signaling pathway through the alpha(v)beta(3) integrins to increase cellular survival. Exposure of colorectal cancer cells to anti-periostin antibodies activates apoptosis and potentiates the effects of 5-fluorouracil chemotherapy. The results demonstrate the growth-promoting properties of periostin, and a possible role of targeting this protein as a therapeutic option in colorectal cancers.
Pancreas
Overexpression of periostin was found in a larger set of pancreatic cancer tissues showing that although the periostin transcript is exclusively expressed in tumour cells, the protein product is only detected in the extracellular matrix adjacent to cancer cells.
Stomach
Periostin was overexpressed in gastric cancer and lymph node metastasis, which suggests that periostin plays an important role in the progression and metastasis of gastric cancer.
Lung
Non Small Cell Lung Cancer patients with periostin expression had significantly poorer survival than the patients without periostin expression (P = 0.0338).
Ovary
Ovarian cancer cells secrete periostin, which can accumulate in malignant ascites of ovarian cancer patiens. Periostin functions as a ligand for alpha(V)beta(3) and alpha(V)beta(5) integrins to support adhesion and migration of ovarian epithelial cells.
Head and Neck
Periostin was highly expressed in head and neck squamous cell carcinoma (HNSCC) in comparison with normal tissues, and the level of periostin expression was well correlated with the invasiveness of HNSCC cases. These findings suggest that periostin plays an important role in the invasion and anchorage-independent growth of HNSCC.
Oral Cavity
Findings suggest that periostin may promote invasion and angiogenesis in oral quamous cell carcinoma, and that periostin can be a strong marker for prediction of metastasis in oral cancer patients.
Neural Tissue
Periostin mRNA expression levels were correlated with tumor progression or prognosis of neuroblastoma.
Periostin as Tumor Supressor
Expression of periostin mRNA is markedly reduced in a variety of human cancer cell lines, suggesting that downregulation of periostin mRNA expression is correlated with the development of human cancers.
Expression of periostin mRNA was detected in 100% (5/5) of normal bladder tissues, it was not detected in 3 human bladder cancer cell lines examined. It was also detected in 81.8% (9/11) of grade 1, 40.0% (4/10) of grade 2 and 33.3% (4/12) of grade 3 bladder cancer tissues, indicating that downregulation of periostin mRNA is significantly related to higher grade bladder cancer (p<0.05). Ectopic expression of periostin gene by a retrovirus vector suppressed in vitro cell invasiveness of the bladder cancer cells without affecting cell proliferation and tumor growth in nude mice. Periostin also suppressed in vivo lung metastasis of the mouse melanoma cell line B16-F10.
Periostin in Circulation
Pancreatic Cancer
Significantly increased levels of periostin were found in the sera of pancreatic cancer patients compared to non-cancer controls.
Non Small Cell Lung Cancer
Serum periostin levels of NSCLC patients had decreased significantly by 4 weeks after the resection of the tumor. The NSCLC patients with high periostin level had significantly poorer survival than the patients with normal periostin level (P = 0.0406).
Thymoma
In thymoma patiens, serum periostin level of stage IV patients was significantly higher than normal control (P=0.0460). These data suggest that serum periostin level may indicate tumor invasion and progression of thymoma.
Breast Cancer
Serum periostin levels were elevated in breast cancer patients presenting with bone metastases compared to similar breast cancer patients without evidence of bone metastasis. Serum periostin levels thus appear to serve as a marker of bone metastasis from breast cancer. Thus, expression of periostin may facilitate tumor cell adhesion to the bone surface. In fact, it was found by in situ RNA hybridization, that the periostin gene was highly expressed in the stromal cells immediately surrounding the tumor, but not within the breast cancer cells themselves.
Preeclampsia
Serum periostin concentrations were elevated in patients with preeclampsia compared with normotensive pregnant women.
| Catalog Number | ¨Product | Clone/Isotype | Reactive sp. | Applications | Size |
|---|---|---|---|---|---|
| RD184045100 | OSTEOBLAST SPECIFIC FACTOR 2 (OSF-2, PERIOSTIN, FASCICLIN-I LIKE) HUMAN | Human | Western blotting, ELISA | 0.1 mg | |
| RD184045100+ | Sheep Polyclonal Antibody | Human | Western blotting, ELISA | 10 x 0.1 mg |