Extracellular matrix oxidation modulates survival, NF-kappaB translocation, and MAPK activity in mesangial cells

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Sergei Kochlatyi1, Nora Gibbons, Joseph Mattana

  • 1Department of Medicine, Long Island Jewish Medical Center, New Hyde Park, New York 11040, USA.

Experimental and Molecular Pathology
|February 5, 2003
PubMed

Insights

Kidney injury can oxidize extracellular matrix, increasing mesangial cell apoptosis. This oxidation impairs cell survival signaling, affecting transcription factors and MAPK pathways.

Area of Science:

  • Nephrology
  • Cell Biology
  • Biochemistry

Background:

  • Inflammatory kidney injury can lead to oxidation of extracellular matrix (ECM) proteins.
  • Oxidized ECM may impair glomerular mesangial cell adhesion and intracellular signaling pathways.

Purpose of the Study:

  • To investigate how ECM oxidation influences mesangial cell apoptosis.
  • To determine the effect of ECM oxidation on the activity of Nuclear Factor-kappaB (NF-kappaB) and Mitogen-Activated Protein Kinase (MAPK) family members (ERK-1,2 and JNK).

Main Methods:

  • Mesangial cells were cultured on oxidized and unmodified ECM.
  • Apoptosis was quantified.
  • Western blot analysis was used to assess levels of phosphorylated ERK-1,2, JNK, and NF-kappaB p65 subunit translocation.

Main Results:

  • Exposure to oxidized ECM significantly increased mesangial cell apoptosis.
  • Phosphorylated ERK-1,2 levels decreased, while phosphorylated JNK levels increased on oxidized ECM.
  • Nuclear translocation of NF-kappaB p65 subunit was reduced in cells cultured on oxidized ECM.

Conclusions:

  • ECM oxidation negatively impacts mesangial cell survival.
  • Altered signaling pathways, including decreased pERK-1,2, increased pJNK, and diminished NF-kappaB activity, are associated with ECM oxidation in kidney injury.

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