Osteopontin (OPN) serves as a multifunctional phosphorylated glycoprotein found throughout different tissue types. The molecule performs cell signal regulation tasks and plays a role in multiple pathological processes. Fibrosis describes a pathological condition where tissues and organs accumulate excess extracellular matrix components resulting in progressive structural changes that cause multiple diseases. Recent research indicates osteopontin functions as both a biomarker and novel therapeutic target for treating fibrotic conditions.
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Physiological Functions of Osteopontin (OPN)
- Regulating immune response: Osteopontin plays an important role in local immune response and promotes the recruitment and activation of macrophages.
- Cell adhesion and migration: By binding to receptors such as integrins, osteopontin can promote cell adhesion and migration, which is crucial in wound healing and tissue repair.
- Signal transduction: Osteopontin affects cell proliferation and apoptosis by activating specific signaling pathways (such as MAPK and NF-κB pathways).
Basic Structure of Osteopontin (OPN)
- Coding gene: SPP1 (secreted phosphoprotein 1)
- Molecular structure: Contains integrin binding sites (such as RGD sequence), heparin binding sites
- Expressing cells: osteoblasts, macrophages, T cells, hepatic stellate cells, renal tubular epithelial cells, etc.
The Relationship between Osteopontin and Fibrotic Diseases
In various fibrotic diseases (such as pulmonary fibrosis, liver fibrosis, renal fibrosis, etc.), the expression level of osteopontin is often significantly increased. Osteopontin participates in the damage and repair process of alveolar epithelial cells, promotes the activation of fibroblasts and the deposition of collagen, thereby aggravating fibrosis. In liver tissue, osteopontin can promote the activation and migration of hepatic stellate cells and promote the production of collagen.
Fig 1. The potential of OPN as a biomarker and novel therapeutic target for fibrosis treatment (Tang, Z., et al. 2023).
In kidney disease, the increase of osteopontin is related to the development of renal tubular cell damage and interstitial fibrosis. Fibrosis is a common pathological process of many chronic diseases (such as cirrhosis, pulmonary fibrosis, renal fibrosis, myocardial fibrosis, etc.), and OPN plays an important role in it:
As a Biomarker of Fibrosis
- In various fibrotic diseases, serum levels and tissue expression of OPN are significantly increased.
- Closely related to the severity of the disease and the degree of tissue sclerosis.
- Can be used as an early predictive indicator or a monitoring tool for disease progression.
Molecular Mechanisms Involved in Fibrosis
Osteopontin promotes the fibrotic process through multiple mechanisms
| Mechanism |
Description |
| Activates fibroblasts |
Promote the secretion of collagen and matrix proteins |
| Induces inflammatory response |
Upregulate inflammatory factors such as TNF-α and IL-6, promote chronic inflammation |
| Synergizes with TGF-β |
Enhance the TGF-β signaling pathway and promote epithelial-mesenchymal transition (EMT) |
| Inhibits cell apoptosis |
Prolong the life of fibrotic cells and increase extracellular matrix deposition |
Research Examples
- Pulmonary fibrosis: OPN is significantly elevated in bronchoalveolar lavage fluid and serum of patients with idiopathic pulmonary fibrosis (IPF), and expression is associated with decreased lung function.
- Liver fibrosis: In hepatitis and non-alcoholic fatty liver disease (NAFLD)-related fibrosis, OPN is associated with the degree of cirrhosis.
- Renal fibrosis: In chronic kidney disease (CKD), OPN is closely associated with the degree of tubulointerstitial fibrosis.
Osteopontin as a potential therapeutic target
The level of osteopontin can reflect the severity of fibrosis and shows certain specificity in different types of fibrotic diseases. Therefore, measuring the concentration of osteopontin may provide valuable information for the early diagnosis and prognosis evaluation of fibrotic diseases.
- Neutralizing antibodies: block the binding of OPN to its receptors (such as integrins, CD44)
- Small molecule inhibitors: interfere with the OPN signaling pathway
- RNA interference technology: silence SPP1 gene expression
- Vaccine strategy: induce the immune system to clear OPN
| Project |
Description |
| Biomarker role |
Predict and monitor the progression of fibrotic diseases |
| Pathogenic mechanism |
Activate inflammation, fibroblasts, enhance TGF-β effects |
| Therapeutic potential |
Can be used as a candidate molecule for targeted therapy |
References
- Tang, Z., et al. The critical role of osteopontin (OPN) in fibrotic diseases. Cytokine & Growth Factor Reviews. 2023, 74: 86-99.
- Icer, M., et al. The multiple functions and mechanisms of osteopontin. Clinical biochemistry. 2018, 59: 17-24.
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