OVEREXPRESSION OF EXTRACELLULAR-MATRIX PROTEINS IN RENAL TUBULOINTERSTITIAL CELLS BY PLATELET-ACTIVATING-FACTOR STIMULATION

Background. One common feature of renal diseases is the development of interstitial fibrosis, but the mechanism of this process remains unde fined. We hypothesized that platelet-activating factor (PAF), a classi cal acute inflammatory mediator involved in the pathogenesis of renal damage, acts on renal tubulointerstitial cells, contributing to the de velopment of fibrosis. For this reason we evaluated the effect of PAF on matrix regulation and cell-growth-related events in tubulointerstit ial cells. Methods. In vitro studies were conducted with two tubuloint erstitial cell lines: renal tubuloepithelial cells (NRK 52E) and inter stitial fibroblasts (NRK 49F). The effect of PAF on extracellular matr ix gene expression was determined by Northern blot. Fibronectin synthe sis was quantified by metabolic labelling and immunoprecipitation. Cel l growth changes were evaluated by fluorescence-activated cell-sorting analysis (cell cycle and size) and total protein content by (3)[H]leu cine incorporation. Results. In renal tubuloepithelial cells and inter stitial fibroblasts, PAF increased fibronectin mRNA expression. PAF-ef fect on the expression of collagen genes differed depending on the cel l type studied. In tubuloepithelial cells there was an increase in typ e I and IV collagen mRNA levels, while only type I collagen was increa sed in fibroblasts. The overexpression of matrix proteins induced by P AF was completely blocked by preincubation of cells with the PAF recep tor antagonist, BN52021. The PAF-induced upregulation of fibronectin e xpression was correlated with the increase in fibronectin synthesis. T hese effects were not associated with an increase in hyperplasia (char acterized by changes in cell cycle) either in tubuloepithelial cells o r in interstitial fibroblasts. Moreover, PAF did not induce tubular hy pertrophy (changes in protein content and cell size). Conclusions. Our data suggest that PAF could be a mediator involved in extracellular m atrix accumulation and, therefore, participate in the formation of ren al interstitial fibrosis.