Phenotypic Modifications of Human Mesangial Cells by Extracellular Matrix: The Importance of Matrix in the Contractile Response to Reactive Oxygen Species

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Abstract
The progression of chronic renal diseases is characterized by the accumulation of extracellular matrix proteins in the glomerulus. The present experiments were designed to analyze the effect of hydrogen peroxide on the contractile and proliferative phenotypes of human mesangial cells grown on different culture substrates: plastic, collagen type I, and collagen type IV. Contraction was analyzed by measuring planar cell surface area and myosin light chain phosphorylation, whereas proliferation was studied by [3H]thymidine incorporation. No changes were detected in the proliferation rate of human mesangial cells grown on different culture substrates, neither under basal conditions nor in the presence of fetal calf serum or H2O2. Cells grown on plastic or collagen did not contract in the presence of H2O2, but cells grown on collagen I elicited a significant contraction with H2O2. Platelet-activating factor induced contraction of human mesangial cells on the three culture substrates. The different contractile responses observed were not due to different degradation rates of H2O2. The present experiments support the importance of extracellular matrix in the response to exogenous stimuli and point to the possibility that patients with changes in the mesangial matrix as a result of chronic renal diseases may have an increased susceptibility to the pathological actions of reactive oxygen species.