uPAR signaling is under par for the podocyte course

Luft, Friedrich C.

doi:10.1007/s00109-012-0980-2

Cited by 6 publications

(10 citation statements)

References 9 publications

(12 reference statements)

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“…In addition, the proteases involved in fibrinolysis might either activate or disarm PARs and can directly modulate cellular function through urokinase plasminogen activator receptor (uPAR) 16,17 . The roles of fibrinolysis and uPAR in renal disease have been reviewed previously 17–19 .…”

Section: The Coagulation Systemmentioning

confidence: 99%

The emerging role of coagulation proteases in kidney disease

2015

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A role of coagulation proteases in kidney disease beyond their function in normal haemostasis and thrombosis has long been suspected, and studies performed in the past 15 years have provided novel insights into the mechanisms involved. The expression of protease-activated receptors (PARs) in renal cells provides a molecular link between coagulation proteases and renal cell function and revitalizes research evaluating the role of haemostasis regulators in renal disease. Renal cell-specific expression and activity of coagulation proteases, their regulators and their receptors are dynamically altered during disease processes. Furthermore, renal inflammation and tissue remodelling are not only associated, but are causally linked with altered coagulation activation and protease-dependent signalling. Intriguingly, coagulation proteases signal through more than one receptor or induce formation of receptor complexes in a cell-specific manner, emphasizing context specificity. Understanding these cell-specific signalosomes and their regulation in kidney disease is crucial to unravelling the pathophysiological relevance of coagulation regulators in renal disease. In addition, the clinical availability of small molecule targeted anticoagulants as well as the development of PAR antagonists increases the need for in-depth knowledge of the mechanisms through which coagulation proteases might regulate renal physiology.

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Section: The Coagulation Systemmentioning

confidence: 99%

The emerging role of coagulation proteases in kidney disease

2015

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“…The urokinase-type plasminogen activator receptor (uPAR) is a multidomain glycoprotein tethered to the cell membrane with a glycosylphosphatidylinositol anchor as the binding site for the extracellular protease urokinase-type plasminogen activator (uPA; urokinase) on the cell surface [11]. However, uPAR interacts with many other proteins, such as integrins, and has pleomorphic functions [12].…”

mentioning

confidence: 99%

“…The complex molecular interactions between uPAR and uPA or other ligands regulate key events during cell adhesion, migration, proliferation, and survival [12]. The plasminogen activation system is important for reorganizing tissues through proteinolysis [11]. uPAR restricts uPA activation to the immediate vicinity of the cell membrane and coordinates the proteinolysis of the extracellular matrix and cell signaling [11].…”

mentioning

confidence: 99%

“…The plasminogen activation system is important for reorganizing tissues through proteinolysis [11]. uPAR restricts uPA activation to the immediate vicinity of the cell membrane and coordinates the proteinolysis of the extracellular matrix and cell signaling [11]. uPAR may also function independently from ligands and engages in lateral interactions with other transmembrane cellular receptors [12].…”

mentioning

confidence: 99%

“…They found that cyclosporin, a calcineurin inhibitor commonly used in the treatment of FSGS, interfered with the nuclear factor of activated T-cell signaling (NFAT), which was also expressed in podocytes [11]. Inducing podocyte-specific NFATc1 increased podocyte uPAR expression and affected cell motility via activation of the β3 integrin in rodent models of glomerular disease (LPS; 5/6 nephrectomized rats) [18].…”

mentioning

confidence: 99%

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