2019Molecular Medicine ReportsOpen access

Dynamic features of liver fibrogenesis and fibrosis resolution in the absence of matrix metalloproteinase‑9

Quanrongzi Wang, Xi-Sheng Liu, Jie Zhang, Ling Lü, Min Feng, Jie Wang

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Abstract

The two‑edged effect of matrix metalloproteinase‑9 (MMP9) makes it difficult to understand its role in liver fibrogenesis and fibrosis resolution. The present study aimed to investigate the dynamic features of liver fibrogenesis and fibrosis resolution in the absence of MMP9. MMP9‑/‑ mice were used to induce liver fibrosis by thioacetamide. The degrees of liver fibrogenesis and fibrosis resolution were designated by the levels of collagen I, III and IV, which were determined via western blotting. Liver injury and the transcriptional levels of MMPs and tissue inhibitor of metalloproteinases (TIMPs) were also determined. It was revealed that, in the absence of MMP9, acute liver injury was attenuated and the expression of collagen was alleviated at the early stage of liver fibrosis, particularly in the first 3 weeks. However, their levels increased to levels as high as those in the control group by week 8. During liver fibrosis resolution, in the absence of MMP9, the ratio of (MMP9 + MMP13)/TIMP1 and the ratio of (MMP2+ MMP14)/TIMP2 were decreased, and the collagen levels were increased. The present study revealed the dynamic features of liver fibrogenesis and fibrosis resolution in the absence of MMP9. The information obtained here will improve current understanding of the effect that MMP9 has in liver fibrogenesis and fibrosis resolution.

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What this paper is about

The two‑edged effect of matrix metalloproteinase‑9 (MMP9) makes it difficult to understand its role in liver fibrogenesis and fibrosis resolution. The present study aimed to investigate the dynamic features of liver fibrogenesis and fibrosis resolution in the absence of MMP9. MMP9‑/‑ mice were used to induce liver fibrosis by thioacetamide. The degrees of liver fibrogenesis and fibrosis resolution were designated by the levels of collagen I, III and IV, which were determined via western blotting. Liver injury and the transcriptional levels of MMPs and tissue inhibitor of metalloproteinases (TIMPs) were also determined. It was revealed that, in the absence of MMP9, acute liver injury was attenuated and the expression of collagen was alleviated at the early stage of liver fibrosis, particularly in the first 3 weeks. However, their levels increased to levels as high as those in the control group by week 8. During liver fibrosis resolution, in the absence of MMP9, the ratio of (MMP9 + MMP13)/TIMP1 and the ratio of (MMP2+ MMP14)/TIMP2 were decreased, and the collagen levels were increased. The present study revealed the dynamic features of liver fibrogenesis and fibrosis resolution in the absence of MMP9. The information obtained here will improve current understanding of the effect that MMP9 has in liver fibrogenesis and fibrosis resolution.

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Available abstract

The two‑edged effect of matrix metalloproteinase‑9 (MMP9) makes it difficult to understand its role in liver fibrogenesis and fibrosis resolution. The present study aimed to investigate the dynamic features of liver fibrogenesis and fibrosis resolution in the absence of MMP9. MMP9‑/‑ mice were used to induce liver fibrosis by thioacetamide. The degrees of liver fibrogenesis and fibrosis resolution were designated by the levels of collagen I, III and IV, which were determined via western blotting. Liver injury and the transcriptional levels of MMPs and tissue inhibitor of metalloproteinases (TIMPs) were also determined. It was revealed that, in the absence of MMP9, acute liver injury was attenuated and the expression of collagen was alleviated at the early stage of liver fibrosis, particularly in the first 3 weeks. However, their levels increased to levels as high as those in the control group by week 8. During liver fibrosis resolution, in the absence of MMP9, the ratio of (MMP9 + MMP13)/TIMP1 and the ratio of (MMP2+ MMP14)/TIMP2 were decreased, and the collagen levels were increased. The present study revealed the dynamic features of liver fibrogenesis and fibrosis resolution in the absence of MMP9. The information obtained here will improve current understanding of the effect that MMP9 has in liver fibrogenesis and fibrosis resolution.

Key concepts: TIMP1, MMP9, MMP2, Matrix metalloproteinase, Thioacetamide, Fibrosis, Liver injury, Hepatic fibrosis

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