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The Protective Role of Autophagy in Matrix Metalloproteinase-Mediated Cell Transmigration and Cell Death in

Chia-Lun Chao1, Chun-Pin Chuang2, Yen-Fen Cheng2

  • 1Division of Cardiology, Department of Internal Medicine, National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei, 10002, Taiwan.

Inflammation
|February 6, 2016
PubMed

Insights

Autophagy protects against high glucose-induced endothelial damage by regulating matrix metalloproteinase-2 (MMP-2). Inhibiting autophagy worsens MMP-2 activity, cell transmigration, and apoptosis in diabetes mellitus research.

Area of Science:

  • Endocrinology and Metabolism
  • Cell Biology
  • Vascular Biology

Background:

  • Diabetes mellitus can lead to vascular endothelial damage, partly mediated by matrix metalloproteinase-2 (MMP-2).
  • The specific role of endothelial autophagy in MMP-2-induced cellular injury under high-glucose conditions remains underexplored.

Purpose of the Study:

  • To investigate the effect of endothelial autophagy on MMP-2-mediated cell transmigration and apoptosis in human umbilical vein endothelial cells (HUVECs) exposed to high glucose (HG).

Main Methods:

  • HG-treated HUVECs were analyzed for autophagy markers (LC3), MMP-2, and apoptosis (PARP) using western blot.
  • MMP-2 activity was assessed via gelatin zymography.
  • The roles of MMP-2 and autophagy were examined using an MMP-2 inhibitor (GM6001) and an autophagy inhibitor (3-methyladenine, 3MA).

Main Results:

  • High glucose stimulation increased LC3-II (autophagy marker), MMP-2 activity, THP-1 transmigration, and cleaved PARP (apoptosis marker) in a time-dependent manner.
  • MMP-2 inhibition reduced MMP-2 activity and THP-1 transmigration.
  • Autophagy inhibition (3MA) decreased LC3-II but increased MMP-2 expression, THP-1 transmigration, and apoptosis.

Conclusions:

  • Autophagy plays a protective role in mitigating MMP-2-mediated cell transmigration and apoptosis in high-glucose-stimulated HUVECs.
  • These findings highlight autophagy as a potential therapeutic target for managing vascular complications in diabetes mellitus.
Keywords:
autophagyendothelial cellshigh glucosematrix metalloproteinasetransmigration

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