THE PATHOLOGICAL MECHANISM OF MATRIX DEGRADATION IN ALCOHOLIC HEPATIC FIBROSIS / 解放军医学杂志

ABSTRACT

To study the mechanism of matrix degradation in alcoholic liver disease (ALD), the liver tissues from 28 patients with ALD were divided into three groups according to their fibrosis degree. The mRNA expression of matrix metalloproteinase 1 (MMP 1), matrix metalloproteinase 2 (MMP 2), membrane type metalloproteinase (MT1 MMP), and tissue inhibitors of metalloproteinase (TIMP) was detected using in situ hybridization method. The results showed that the cells with positive MMP 1, MMP 2, MT1 MMP, and TIMP mRNA staining were mainly located around the fibrotic central veins, walls of sinusoids, and portal triads. These positive cells were the cells of hepatic sinusoidal walls and a few hepatocytes, meanwhile, some cells expressed both the MMP 2 and the MT 1MMP mRNA. The positive cells of the MMP 2, MT1 MMP, and TIMP mRNA increased in parallel with the severity of fibrosis, whereas the expression of MMP 1 mRNA decreased. These changes were observed predominantly in moderate fibrosis group. There findings demonstrated that down regulation of MMP 1 expression and up regulation of TIMP expression might be involved in excessive accumulation of extracellular matrix (ECM) in ALD. MMP 2 might collaborate with MT1 MMP in degradation of ECM. thereby contributing to fibrosis of central veins.Hepatic stellate cells might be the main cellular source of MMP 1, MMP 2, MT1 MMP and TIMP in ALD.