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Kupffer-derived matrix metalloproteinase-9 contributes to liver fibrosis resolution

Min Feng1, Jie Ding1, Min Wang2

  • 1Department of General Surgery, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, China.

International Journal of Biological Sciences
|July 11, 2018
PubMed

Insights

Kupffer cells (KCs) are crucial for liver fibrosis resolution. KC-derived matrix metalloproteinase-9 (MMP9) significantly enhances this process, offering potential therapeutic targets for liver disease.

Area of Science:

  • Hepatology
  • Immunology
  • Biochemistry

Background:

  • Kupffer cells (KCs) produce matrix metalloproteinases (MMPs) involved in liver fibrosis resolution.
  • The specific role of MMP9, a major KC-derived MMP, in this process is not well understood.

Purpose of the Study:

  • To investigate the role of KC-derived MMP9 in resolving liver fibrosis.
  • To determine if MMP9 is essential for the fibrolytic activity of KCs.

Main Methods:

  • Rodent liver fibrosis was induced using thioacetamide (TAA) and resolution was initiated by TAA withdrawal.
  • The function of KC-derived MMP9 was assessed via adoptive transfer of KCs with or without MMP9.
  • Levels of ALT, cytokines, and mRNA for MMPs and TIMPs were analyzed during fibrosis regression.

Main Results:

  • KC depletion delayed liver fibrosis resolution and prolonged wound healing.
  • Adoptive transfer of wild-type KCs promoted resolution more effectively than MMP9-deficient KCs.
  • KC absence reduced MMPs mRNA and increased TIMPs mRNA, effects partially restored by WT KCs.

Conclusions:

  • KC-derived MMP9 plays a critical role in liver fibrosis resolution.
  • MMP9 is essential for the fibrolytic function of KCs.
  • Targeting KC-derived MMP9 may offer a novel therapeutic strategy for liver fibrosis.
Keywords:
Kupffer cellsfibrosis resolutionliver fibrosismatrix metalloproteinase

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