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. 2020 Jul 11;21(14):4906. doi: 10.3390/ijms21144906

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© 2020 by the authors.

Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).

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Representative mechanism of matrix metalloproteinase (MMP) and tissue inhibitor of metalloproteinase (TIMP) in liver fibrosis. Red arrows indicate activation, blue arrows indicate inhibition. TGF-β1, transforming growth factor β1. TIMP-1 is produced by activated stellate cell, hepatocyte, and Kupffer cell. TIMP-1 is regulated by TGF-β1 and inhibits collagenase (MMP-1, 8, 13) and apoptosis of hepatic stellate cell, causing liver fibrosis and cirrhosis. TIMP-2 is produced by activated stellate cell and Kupffer cell. TIMP-2 inhibits MMP-2 and also activates pro-MMP-2, causing degradation of normal liver matrix.