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Urinary matrix metalloproteinase -8, -9, -14 and their regulators (TRY-1, TRY-2, TATI) in patients with diabetic

Anneli Lauhio1, Timo Sorsa, Ravi Srinivas

  • 1Helsinki University Central Hospital, Department of Medicine, Division of Infectious Diseases, Helsinki, Finland. anneli.lauhio@hus.fi

Annals of Medicine
|April 23, 2008
PubMed

Insights

Diabetic nephropathy (DNP) involves increased urinary matrix metalloproteinases (MMPs) and trypsins. A trypsin-MMP cascade may drive DNP pathogenesis, suggesting potential therapeutic targets like MMP inhibitors.

Area of Science:

  • Biochemistry
  • Nephrology
  • Enzymology

Background:

  • Diabetic nephropathy (DNP) is a complication of diabetes.
  • Matrix metalloproteinase-9 (MMP-9) is implicated in DNP development.
  • Urinary enzyme profiles in DNP require further investigation.

Purpose of the Study:

  • To investigate urinary levels, forms, and activation of MMP-8, MMP-9, MMP-14, trypsin-1, trypsin-2, and TATI in DNP patients.
  • To explore the relationship between these enzymes and DNP pathogenesis.
  • To identify potential diagnostic or therapeutic targets for DNP.

Main Methods:

  • Western blotting and gelatin zymography for MMP analysis.
  • Time-resolved immunofluorometric assays for trypsin and TATI quantification.
  • Comparative analysis of urinary samples from DNP patients and healthy controls.

Main Results:

  • Significantly higher total MMP-8, active MMP-9 proportion, and gelatinolytic activity in DNP patients.
  • Increased active polymorphonuclear neutrophil (PMN)-type MMP-8 and soluble MMP-14 in DNP urine.
  • Elevated trypsin-1 and trypsin-2 levels, with significant associations between MMP activation and TRY-2.

Conclusions:

  • A trypsin-matrix metalloproteinase cascade is suggested to be involved in DNP pathogenesis.
  • Urinary MMPs and trypsins may serve as biomarkers for DNP.
  • MMP inhibitors could represent a novel therapeutic strategy for DNP.

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