Senescent hepatocyte secretion of matrix metalloproteinases is regulated by nuclear factor-κB signaling.

Aims: Cellular senescence and matrix metalloproteinases (MMPs) play an important role in liver diseases. The source and regulating factors of MMPs in senescent hepatocytes are not known. We investigated whether senescent hepatocytes secreted MMPs and if this was regulated by nuclear factor (NF)-κB.

Materials And Methods: The TGF-α transgenic mouse hepatocyte line AML12 was treated with HO to induce senescence. NF-κB signaling was examined by Western blotting and luciferase reporter assays. Quantitative reverse transcription polymerase chain reaction was used to evaluated expression of MMP-2, -9 and -13.

Key Findings: AML12 cells treated with HO showed the characteristic morphology of senescence. The activity of NF-κB and expression of MMP-2, -9 and -13 were increased in senescent AML12 cells. The NF-κB inhibitor BAY 11-7082 decreased the levels of MMPs.

Significance: These results suggest that senescent hepatocytes are involved in the pathology of liver diseases through remodeling the extracellular matrix.