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Recent Advances in Thrombosis and Hemostasis 2008 pp 336–347Cite as

Role of Fibrinolysis in Hepatic Regeneration

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Abstract

Liver regeneration has been studied intensively, and it has been revealed that the major enzymes that degrade the extracellular matrix (ECM) are matrix metal-loproteinases and fibrinolytic enzymes. This proteolytic activity regulates ECM assembly, editing of excess ECM components, remodeling of the ECM structure, and release of growth factors and cytokines during the liver regeneration process. The fibrinolytic factors act in the liver regeneration process in the following two ways: activation of growth factors and degradation of ECM components. Studies on these points have been drastically advanced by the use of genetic all-deficient mice. Plasminogen (Plg) and urokinase-type plasminogen activator (u-PA) are bound to hepatocytes from mouse liver. Binding of Plg to hepatocytes impairs the inhibitory effect of α2-antiplasmin (α2-AP); that is, activation of Plg by Plg activator (PA) in the presence of hepatocytes is more enhanced than in the absence of hepatocytes. u-PA activates hepato cyte growth factor (HGF) and induces the proliferation of hepatocytes. Because Plg cleared ECM in mouse models, the loss of Plg showed a delay in liver regeneration. Thus, fibrinolytic factors are thought to act in two ways in the process of healing and regeneration after liver injury. The u-PA/PA inhibitor type-1 (PAI-1) system regulates the proliferation of hepatocytes by controlling HGF activation. The plasmin/α2-AP system regulates the microenvironment of liver regeneration by controlling ECM degradation. It is anticipated that in the future the regulation of proteases, which involve mainly fibrinolytic factors, will be a form of regenerative medicine for the liver.

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Authors and Affiliations

  1. Department of Physiology, Kinki University School of Medicine, 377-2 Ohnohigashi, Osakasayama, Osaka, 589-8511, Japan

    Kiyotaka Okada, Shigeru Ueshima & Osamu Matsuo

  2. Department of Food Science and Nutrition, Kinki University School of Agriculture, 3327-204 Nakamachi, Nara, Nara, 631-8505, Japan

    Shigeru Ueshima

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  1. Kiyotaka Okada
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Editors and Affiliations

  1. Department of Pathology, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan

    Kenzo Tanaka M.D., Ph.D. (Professor Emeritus) (Professor Emeritus)

  2. Department of Biochemistry, University of Washington, J317 Health Science Center, Box 357350, Seattle, WA, 98195, USA

    Earl W. Davie Ph.D. (Professor) (Professor)

  3. School of Medicine, Internal Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan

    Yasuo Ikeda M.D., Ph.D. (Professor) (Professor)

  4. Department of Biology, Kyushu University, 6-10-1 Hakozaki, Higashi-ku, Fukuoka, 812-8581, Japan

    Sadaaki Iwanaga Ph.D. (Professor Emeritus) (Professor Emeritus)

  5. Department of Medicine, Nagoya University, 26 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan

    Hidehiko Saito M.D., Ph.D. (Professor Emeritus) (Professor Emeritus)

  6. Pathophysiological and Experimental Division, Department of Pathology, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan

    Katsuo Sueishi M.D., Ph.D. (Professor) (Professor)

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Okada, K., Ueshima, S., Matsuo, O. (2008). Role of Fibrinolysis in Hepatic Regeneration. In: Tanaka, K., Davie, E.W., Ikeda, Y., Iwanaga, S., Saito, H., Sueishi, K. (eds) Recent Advances in Thrombosis and Hemostasis 2008. Springer, Tokyo. https://doi.org/10.1007/978-4-431-78847-8_24

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