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

Abstract

AimsCellular 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 methodsThe TGF-α transgenic mouse hepatocyte line AML12 was treated with H2O2 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 findingsAML12 cells treated with H2O2 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. SignificanceThese results suggest that senescent hepatocytes are involved in the pathology of liver diseases through remodeling the extracellular matrix.