Periostin

Periostin (POSTN, PN, or osteoblast-specific factor OSF-2) is a is_associated_with::protein that in humans is encoded by the POSTN is_associated_with::gene. Periostin functions as a ligand for alpha-V/beta-3 and alpha-V/beta-5 is_associated_with::integrins to support adhesion and migration of epithelial cells.

Periostin is a is_associated_with::gla domain vitamin K dependent factor.

Function
Periostin is a secreted extracellular matrix protein that was originally identified in cells from the mesenchymal lineage (is_associated_with::osteoblasts, osteoblast-derived cells, the periodontal ligament, and is_associated_with::periosteum). It has been associated with the is_associated_with::epithelial-mesenchymal transition in cancer and with the differentiation of mesenchyme in the developing heart. This protein shares a homology with fasciclin I, a secreted cell adhesion molecule found in insects. In many cancers, periostin binds to is_associated_with::integrins on cancer cells, activating the Akt/PKB- and FAK-mediated signaling pathways. This leads to increased cell survival, invasion, is_associated_with::angiogenesis, is_associated_with::metastasis, and the epithelial-mesenchymal transition.

In humans and mice, periostin undergoes alternative splicing in its C-terminal region, resulting in specific is_associated_with::isoforms that can be observed in a broad range of cancers such as pancreatic, colon, and breast cancer.

While periostin plays a wide variety of roles in tissue development along with disease, its function in tissue remodeling as a response to injury is a common underlying role in these different mechanisms. Periostin is transiently upregulated during cell fate changes, whether they are related to alterations in physiology or to pathological changes. It influences is_associated_with::extracellular matrix restructuring, tissue remodeling, and the epithelial-mesenchymal transition, all of which can be related to tissue healing, development, and disease. Thus, it functions as a mediator, balancing appropriate and inappropriate responses to tissue damage.

In valvular heart disease
Periostin plays a critical role in the development of is_associated_with::cardiac valves and in degenerative is_associated_with::valvular heart disease. While periostin usually is localized to the subendothelial layer in healthy heart valves, its levels are highly increased in infiltrated inflammatory cells and is_associated_with::myofibroblasts in angiogenic areas in atherosclerotic and rheumatic valvular heart disease in humans. Periostin has also been shown to increase the secretion of is_associated_with::matrix metalloproteinase from valvular intestinal cells, endothelial cells, and macrophages. It is thought that periostin plays a role in cardiac valve complex degeneration by inducing both angiogenesis and matrix metalloproteinase production.

In tissue regeneration and healing
As a matricellular protein, periostin is also important for tissue regeneration. In healthy human skin, periostin is expressed at basal levels and is expressed in the epidermis and hair follicles along with is_associated_with::fibronectin and is_associated_with::laminin γ2. Periostin is involved in wound healing, helping for the wound to heal faster than when periostin is not present in cells. This delay in wound closure is also associated with a delay in re-epithelialization and a reduction in the proliferation of is_associated_with::keratinocytes. Periostin localizes to the extracellular compartment of cells during tissue remodeling associated with wound repair. It may also promote injury closure by facilitating the activation, differentiation, and contraction of is_associated_with::fibroblasts. However, the increase in periostin expression associated with tissue regeneration post-injury is transient, starting a few days post-injury, peaking after seven days post-injury, and decreasing afterwards.

In asthma
Periostin is associated with is_associated_with::asthma, a fact that is exploited by the experimental asthma medication is_associated_with::lebrikizumab.

In cancer
Periostin over-expression was reported in several types of cancer, most frequently in the environment of tumor cells. Recent evidence shows that periostin is a component of the extracellular matrix expressed by fibroblasts in normal tissues and stroma of primary tumor. The metastatic colony formation requires the induction of periostin in the foreign stroma by the infiltrating cancer cells. Periostin production is upregulated in lung fibroblasts by either TGF-β2 or TGF-β3, the latter being secreted by infiltrating cancer stem cells (in MMTV-PyMT mouse breast cancer model)

Periostin has been shown to be highly upregulated in is_associated_with::glioblastomas (grade IV gliomas) compared to the normal brain. In gliomas, periostin expression levels correlate directly with tumor grade and recurrence, and inversely with survival. It has been shown that glioma stem cells in glioblastomas secrete periostin, which recruits M2 tumor-associated is_associated_with::macrophages from peripheral blood to the tumor environment via αvβ3 integrin signaling. These M2 TAMs differentiate from monocytes once they enter the tumor tissue. Through this recruitment mechanism, periostin supports tumor progression, as M2 tumor-associated macrophages are tumor-supportive and immunosuppressive. In this environment, periostin functions as a is_associated_with::chemoattractant, promoting both migration and invasion of macrophages and monocytes into glioblastomas in a dose-dependent manner. Clinically, periostin-associated gene signatures, which are predominated by secreted and matrix proteins, correspond to patient prognosis and malignancy. Given its features related to glioblastoma progression, periostin is a marker of is_associated_with::glioma malignancy as well as recurrence of tumors, making it a possible target for therapy that continues to be studied and explored.

1 (cDNA POSTN/cDNA ACTB) × 104