Extracellular matrix oxidation modulates survival, NF-kappaB translocation, and MAPK activity in mesangial cells.
Inflammatory injury to the kidney may oxidize extracellular matrix proteins. These changes appear to impair adhesion of glomerular mesangial cells and might impact signaling mechanisms in these cells. In this study we evaluated how extracellular matrix oxidation could modulate the development of apoptosis as well as the activity of the transcription factor NF-kappaB and that of the MAPK family members ERK-1,2 and JNK. Exposure of mesangial cells to oxidized matrix enhanced the percentage of apoptotic cells. Western blot analysis revealed diminished levels of the phosphorylated form of ERK-1,2 in cells on oxidized matrix, while levels of phosphorylated JNK were increased. Cells on unmodified matrix were found to have rapid translocation of the p65 subunit of NF-kappaB, which was attenuated in cells on oxidized matrix. These findings suggest that extracellular matrix oxidation may impair survival of mesangial cells in association with decreased levels of pERK-1,2, increased levels of pJNK, and diminished nuclear translocation of the transcription factor NF-kappaB.
Kochlatyi
Sergei
S
Department of Medicine, Long Island Jewish Medical Center, New Hyde Park, New York 11040, USA.
Gibbons
Nora
N
Mattana
Joseph
J
D021581:Active Transport, Cell Nucleus / Q000502:physiology; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D048429:Cell Size; D002470:Cell Survival; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free; D004268:DNA-Binding Proteins / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism*; D005920:Glomerular Mesangium / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D010084:Oxidation-Reduction; D015398:Signal Transduction / Q000502:physiology*; D051996:Transcription Factor RelA
D016895:Culture Media, Serum-Free; D004268:DNA-Binding Proteins; D016328:NF-kappa B; D051996:Transcription Factor RelA; D020928:Mitogen-Activated Protein Kinases