Serum soluble urokinase-type plasminogen activator receptor as an indicator of poor clinical outcome in inflammatory diseases
Urokinase, also known as the urokinase-type plasminogen activator (uPA)
- is a serine protease, synthesized in large amounts in the kidney and present in blood and extracellular matrix (ECM)
- its main substrate, plasminogen, is an inactive form of the serine protease plasmin
- thee activation of plasmin by the proteolytic activity of uPA on plasminogen leads to thrombolysis or matrix degradation (depending on the environment)
- uPA, apart from its thrombolytic properties, is also able to affect cell migration, adhesion, and mitosis
- in the ECM, uPA binds to its cellular receptor, uPAR
- uPAR is a membrane-bound 45-55 kDa protein with 3 extracellular domains (D1, D2, and D3) linked to a glycosylphosphatidylinositol (GPI) anchor in the cell membrane
- when uPAR is cleaved by proteases from the cell surface (at the GPI anchor), a soluble form of uPAR (suPAR) is released
- in healthy individuals, suPAR levels are quite stable in both blood and urine and suPAR levels in urine, adjusted according to urine creatinine and correlate positively and strongly with plasma suPAR-levels. Also, circadian suPAR plasma-concentrations (measured 24 h, 20 min intervals) appear to be stable
- however, when inflammatory cells are activated by cytokines
- the expression of uPAR can be up-regulated, thus elevating the serum levels of suPAR
- has been demonstrated that the serum concentrations of suPAR can be increased during inflammatory and infectious diseases, such as arthritis, liver fibrosis, human immunodeficiency virus (HIV) infection, bacterial infection and malaria, reflecting the activation of the immune system
- emerging evidence indicates that suPAR is involved in various biological functions, including cell adhesion, migration, and chemotaxis, and its increased level is associated with poor clinical outcomes in various inflammatory diseases, such as sepsis, bacteremia, and SIRS
- soluble urokinase plasminogen activator receptor is of good predictive value for severe acute pancreatitis (SAP) risk and may serve as a potential biomarker for disease severity, inflammation, and inhospital mortality in SAP patients
Reference:
- Ni W, Han Y, Zhao J, Cui J, Wang K, Wang R, Liu Y. Serum soluble urokinase-type plasminogen activator receptor as a biological marker of bacterial infection in adults: a systematic review and meta-analysis. Sci Rep. 2016 Dec 19;6:39481.
- Zhang Q, Li L, Chen H, Zhang G, Zhu S, Kong R, Chen H, Wang G, Sun B. Soluble urokinase plasminogen activator receptor associates with higher risk, advanced disease severity as well as inflammation, and might serve as a prognostic biomarker of severe acute pancreatitis. J Clin Lab Anal. 2020 Mar;34(3):e23097.