Role of coagulation and fibrinolysis in lung and renal fibrosis

Summary

Elevated procoagulant and suppressed fibrinolytic activities are regularly encountered in different forms of clinical and experimental fibrosis of the lungs and the kidneys. Although primarily serving to provide a provisional matrix of repair largely consisting of fibrin and fibronectin, the involved procoagulant serine proteases and protease inhibitors may also exert distinct cellular downstream signaling events modifying the fibrotic reponse.

In this review, evidence for an impaired regulation of coagulation and fibrinolysis factors in clinical and experimental lung and renal fibrosis is provided and the role of PAR (protease activated receptor) induced profibrotic and HGF (hepatocyte growth factor) elicited antifibrotic cellular events is worked out. In view of experiments obtained in animal models of lung and renal fibrosis, the potential therapeutic usefulness of anticoagulant or profibrinolytic strategies is discussed.

Zusammenfassung

Bei Patienten mit fibrosierenden Lungen- und Nierenerkrankungen ist eine deutliche Verschiebung der lokalen hämostaseologischen Balance zu Gunsten einer vermehrten Gerinnung zu verzeichnen. Obgleich die vermehrte Bereitstellung von TF/FVII, FX, Thrombin und PAI-1 einerseits und die Suppression von u-PA andererseits zunächst vor allem die Entstehung einer primären Matrix der Wundheilung begünstigen, könnten diese Faktoren über die Aktivierung von PAR (protease activated receptor) und HGF (hepatocyte growth factor) pro- bzw. antifibrotische Signalkaskaden wesentlich beeinflussen.

In diesem Review wird der aktuelle Kenntnisstand zu Veränderungen des Gerinnungs- und Fibrinolysesystem in Patienten und tierexperimentellen Modellen mit fibrosierenden Lungen- und Nierenerkrankungen dargelegt. Die Beteiligung PAR- bzw. HGF-abhängiger Signaltransduktionskaskaden bei der Modulation der Fibroseantwort wird gezeigt und die therapeutische Beeinflussung der hämostaseologischen Balance zur Behandlung der Fibroseantwort diskutiert.

Keywords

Coagulation - fibrinolyis - fibrosis

Schlüsselwörter

Gerinnung - Fibrinolyse - Fibrose

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