Periostin (POSTN) is a specialized matricellular protein secreted into the extracellular matrix (ECM), the space surrounding cells. This protein acts as an important communication link, managing interactions between cells and the structural scaffold that supports them. Periostin is not a structural component itself, but rather a regulator that helps organize and maintain tissue integrity. While present in low amounts in healthy adult tissues, its presence increases dramatically in response to injury or disease, making it a subject of medical interest due to its involvement in tissue remodeling and chronic diseases.
Primary Functions in Connective Tissue
Periostin’s function centers on building and maintaining collagen-rich connective tissues throughout the body. It is found predominantly in areas subjected to mechanical stress, such as the periodontal ligament, tendons, heart valves, and bone. This protein is necessary for the proper development and maturation of these tissues, particularly during early life.
Periostin directly participates in collagen fibrillogenesis, the assembly of individual collagen molecules into robust, banded fibers. It regulates fiber diameter and facilitates cross-linking, which determines the tissue’s tensile strength and biomechanical properties. Without Periostin, connective tissues exhibit reduced strength and altered structural organization.
In healthy adults, Periostin expression is low, but it is quickly upregulated by mechanical cues or during tissue maintenance. By interacting with cell-surface receptors, Periostin mediates cell adhesion and migration, helping to position cells correctly within the ECM. This ensures that the structural components remain organized and capable of withstanding physical forces.
Role in Asthma and Allergic Responses
Periostin is involved in the chronic inflammation characteristic of severe asthma. Its production is strongly induced by Type 2 helper T-cell (Th2) cytokines, specifically Interleukin-4 (IL-4) and Interleukin-13 (IL-13). This makes Periostin a key downstream mediator of Type 2 inflammation, often referred to as T2-high asthma.
In the airways of asthmatic patients, elevated Periostin levels contribute to pathological changes known as airway remodeling. It promotes the thickening of the subepithelial basement membrane, a form of fibrosis that stiffens the airway walls and reduces lung function. Periostin also supports the recruitment and adhesion of eosinophils by acting as an attachment site in the extracellular matrix.
The protein is also implicated in other T2-high conditions like atopic dermatitis (eczema). In the skin, Periostin interacts with cells to amplify the allergic inflammatory loop, promoting the persistence of the chronic condition. Because of its direct link to IL-13 signaling, Periostin serves as a systemic indicator of T2-high inflammation that can be measured in the blood.
Involvement in Structural Repair and Fibrosis
Beyond its role in allergic inflammation, Periostin contributes to fibrosis following non-allergic tissue damage. When an organ sustains an injury, Periostin expression is rapidly increased as part of the body’s attempt at structural repair. This upregulation is driven by growth factors like Transforming Growth Factor-beta (TGF-β), which activate fibroblasts to produce excessive matrix material.
In the heart, Periostin levels surge after a myocardial infarction, where its function is to stabilize the damaged tissue. However, this reparative process can become excessive, leading to cardiac fibrosis, where stiff scar tissue replaces functional muscle. This over-deposition of matrix material impairs the heart’s ability to pump effectively.
Similarly, in chronic lung diseases like Idiopathic Pulmonary Fibrosis, Periostin is highly expressed in areas of active scarring known as fibroblastic foci. Here, it drives the continuous production and organization of a dense, unyielding extracellular matrix. The protein’s action shifts the normal repair mechanism into a sustained, pathological process that progressively destroys the organ’s architecture.
Clinical Measurement and Therapeutic Potential
Periostin’s involvement in T2-high inflammation and fibrosis has established its value as a clinical biomarker. Periostin levels can be measured in a patient’s blood serum, which is particularly useful in asthma to identify patients with the T2-high phenotype.
Serum Periostin levels can predict which patients are most likely to respond favorably to specific biologic therapies, such as monoclonal antibodies that target IL-13. By using Periostin as a guide, clinicians can better select tailored treatments, optimizing the chance of a successful outcome. This predictive capacity aids personalized medicine in respiratory care.
Given its role in driving both allergic inflammation and structural scarring, Periostin is a target for new drug development. Researchers are investigating monoclonal antibodies designed to neutralize circulating Periostin to interrupt disease-promoting signals. Inhibiting Periostin could potentially reduce airway remodeling in asthma and limit the excessive scarring seen in fibrotic diseases of the heart and lungs.