Inflammation, Damage Repair and Liver Fibrosis - Role of Cytokines and Different Cell Types

Zusammenfassung

Die Leberfibrose ist definiert als exzessive Ablagerung von extrazellulärer Matrix. Sie stellt die Hauptkomplikation einer chronischen Leberschädigung dar und das Endstadium, die Leberzirrhose ist mit einer ausgeprägten Morbidität und Mortalität vergesellschaftet. Für die Akkumulation von extrazellulärer Matrix im Rahmen der Leberfibrose und Leberzirrhose sind unterschiedliche Zelltypen verantwortlich, die einen myofibroblastenähnlichen Phänotyp annehmen - die im Disse’schen Raum lokalisierten hepatischen Sternzellen, portale Fibroblasten und Myofibroblasten aus den periportalen und perizentralen Gebieten. Weitere Studien legen auch eine besondere Rolle von Myofibroblasten aus dem Knochenmark nahe. Obwohl Unterschiede zwischen den Zelltypen hinsichtlich myofibroblastischer Differenzierung, Aktivierung und „Deaktivierung” beschrieben wurden, ist in den meisten Fällen eine weitere Sicherung der Daten erforderlich, insbesondere im Hinblick auf biologische und biochemische Charakterisierung, ihre Interaktionen mit inflammatorischen Zellen und der Zytokinzusammensetzung, die zu ihrer Aktivierung oder ihrem Zelltod führt. Diese Daten sind essenziell, um die Mechanismen der fortschreitenden Entwicklung einer exzessiven Vernarbung in der Leber wie auch die Fähigkeit der Leber zur Gewebereparatur und Regenration zu verstehen. Nur so kann der Stellenwert von möglichen Behandlungsschemata zur spezifischen und effizienten Beeinflussung der Zellen, die für die Entwicklung einer Leberfibrose/Leberzirrhose wie auch für die Leberregeneration verantwortlich sind, abgeschätzt werden.

Abstract

Liver fibrosis is defined as an excessive deposition of extracellular matrix. It is the main complication of chronic liver damage and its endpoint, the liver cirrhosis, is responsible for impressive morbidity and mortality. The accumulation of extracellular matrix proteins in liver fibrosis and cirrhosis is due to different cell types which acquire a myofibroblastic phenotype - the hepatic stellate cells, located in the space of Disse, portal fibroblasts as well as myofibroblasts of the portal and pericentral areas. Further studies also suggest an impressive role of bone marrow-derived myofibroblasts. Differences have been reported between the two cell populations with respect to myofibroblastic differentiation, activation and “deactivation”, proliferation and apoptosis. However, in most cases additional confirmation may be required; thus the biological and biochemical characterization of these cells, their interactions with inflammatory cells and the cytokine environment leading to their activation or cell death are essential to understand the mechanisms underlying the progressive development of excessive scarring in the liver as well as the ability of the liver for tissue repair and regeneration. All this information is required to estimate the value of already suggested possible treatments to specifically and efficiently target the cells responsible for the development of liver fibrosis/cirrhosis and as well as for liver regeneration.

Schlüsselwörter

Leber - Fibrose - Zirrhose - HSC - Myofibroblasten - Zytokine

Key words

liver - fibrosis - cirrhosis - HSC - myofibroblasts - cytokines

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