Soluble urokinase plasminogen activator receptor—A valuable biomarker in systemic lupus erythematosus?

Abstract

The expression of uPAR is mainly regulated by growth factors and pro-inflammatory cytokines like basic fibroblast growth factor, epidermal growth factor, tumor necrosis factor, interleukin ( suPAR as a clinical marker of inflammation and organ damagePlasma membrane expression of uPAR as well as the levels of circulating suPAR have been investigated in relation to a broad range of conditions and suPAR has been referred to as a "molecular crystal ball" due to its prognostic value in diseases like tuberculosis, HIV, sepsis and cancer [2,6,13,26,58,59]. Further, it has been reported that it reflects overall immune activation and systemic inflammation [2]. suPAR has also emerged as a potential biomarker of fibrosis in chronic liver diseases of diverse etiology [10,11,[60][61][62].Recently, suPAR attracted significant attention in primary focal segmental glomerulosclerosis (FSGS). data from this pilot study revealed significantly higher suPAR levels among patients with moderately or highly elevated SDI after study inclusion, compared to patients without SDI increase (Figure 2).Furthermore, there were higher death rates among patients in the two groups with SDI increase (Figure 2). However, it is well known that present organ damage predicts further organ damage [17,100], and thus, adjustment for SDI at baseline should be performed to reduce the risk of bias. A stepwise linear multiple regression analysis was therefore performed to evaluate the impact of suPAR on future SDI increase. After adjusting for age, sex and SDI at study inclusion, we found suPAR levels to have a significant impact on future SDI increase (p = 0.005, standardized β = 0.20) whereas SDI at study inclusion was excluded from the model. Since recent studies have revealed an inverse correlation between serum suPAR and glomerular filtration [67,68,96], we also included estimated glomerular filtration (eGFR) (calculated by the 4-variable Modification of Diet in Renal Disease StudyGroup formula [101]) in the analysis, but eGFR was not retained in the model. From these results, we suggest that suPAR can actually predict organ damage independent of present SDI score or eGFR, but that a prospective study examining the association between suPAR levels at the time of diagnosis with future SDI would be preferable.In line with these findings, elevated suPAR levels have previously been demonstrated to associate with the risk of developing cancer, cardiovascular disease and type 2 diabetes later in life in the general population [7]. Importantly, these associations were independent of CRP, which is known for its predictive value in cardiovascular disease [7,102].7 Potential roles of suPAR in SLE pathogenesisAssessment of circulating suPAR levels at the clinical laboratory could possibly become a future way to estimate organ damage in SLE, and suPAR would be an even more appealing biomarker candidate if the levels could be mechanistically linked to the disease. The pathogenesis of SLE is notoriously complex and not fully understood, but includes disturbances in t...

Circulating Soluble Urokinase-Type Plasminogen Activator Receptor in Obstructive Sleep Apnoea

“…Obstructive sleep apnoea is associated with heightened systemic inflammation, theoretically contributing to higher uPAR expression [11,[13][14][15]. However, the cleavage of uPAR may be slower in OSA due to decreased levels of uPA [8] and plasmin [5,6,23].…”

“…In addition, OSA is associated with decreased levels of transforming growth factor-β [8], an inducer of uPAR transcription [29,30]. These studies suggest that although uPAR expression may be upregulated by systemic inflammation in OSA [11,[13][14][15]; this is counterbalanced by the reduced cleavage.…”

“…It is produced upon cleavage of the membrane-bound urokinase-type plasminogen activator receptor (uPAR). The cleavage is facilitated by urokinase-type plasminogen activator (uPA), plasmin, matrix metalloproteases, neutrophil elastase and cathepsin G [11]. The urokinase receptor (also known as uPAR) is expressed by endothelial cells, macrophages, monocytes, neutrophils, lymphocytes, smooth muscle cells and fibroblasts [12,13].…”

“…The urokinase receptor (also known as uPAR) is expressed by endothelial cells, macrophages, monocytes, neutrophils, lymphocytes, smooth muscle cells and fibroblasts [12,13]. It is upregulated under infections and as an effect of pro-inflammatory cytokines [11,[13][14][15], while suPAR contributes to plasminogen activation, cell adhesion, chemotaxis and immune cell activation [16]. However, uPAR also acts as a scavenger receptor for uPA, inhibiting its actions [17].…”

Soluble urokinase-type plasminogen activator receptor and urokinase-type plasminogen activator receptor contribute to chemoresistance in leukemia

“…suPAR is detectable in low, but constant concentrations in the plasma of healthy individuals (2,3). Increased suPAR levels have been observed in numerous pathological conditions including infection (4-6), autoimmune diseases (7,8) and neoplastic diseases (9), as well as during pregnancy (10) and pregnancy-associated disorders (11,12). Preliminary studies indicate that increased plasma suPAR concentrations were observed in patients with non-small-cell lung (13), advanced breast and colorectal (14) and ovarian cancer (15).…”