RADIATION-INDUCED ALTERATION OF RAT MESANGIAL CELL TRANSFORMING GROWTH-FACTOR-BETA AND EXPRESSION OF THE GENES ASSOCIATED WITH THE EXTRACELLULAR-MATRIX

We hypothesized that the altered mesangial cell phenotype observed in radiation nephropathy reflects, at least partly, radiation-induced cha nges in expression of the genes associated with transforming growth fa ctor-beta (TGF-beta) and extracellular matrix (ECM). To test this hypo thesis, rat mesangial cells were used between passages 7 and 11 after primary isolation from glomeruli. Cells were placed in serum-free medi um 24 h prior to irradiation and irradiated with single doses of 5-20 Gy Cs-137 gamma rays; control cells received sham irradiation. After i rradiation, the cells were maintained in serum-free medium for up to 4 8 h postirradiation. Total RNA was isolated, and Northern analysis was performed using cDNA probes for TGF-beta(1), beta(2) and beta(3) and several ECM genes. Irradiation resulted in isoform-specific alteration s in TGF-beta mRNA; TGF-beta(1) levels showed a dose-independent incre ase 24-48 h postirradiation; TGF-beta(3) mRNA levels showed a progress ive dose-independent decrease over the same period, decreasing to leve ls approximately 25% of those seen in controls. These changes were ass ociated with a concomitant increase in levels of mRNA expressed by gen es for the components of the ECM; no changes were observed in TGF-beta (2), collagen I, collagen III or decorin. Thus radiation can alter mes angial cell TGF-beta and the expression of the genes involved in ECM, although the nature of this alteration varies for the TGF-beta isoform s and specific ECM genes. (C) 1996 by Radiation Research Society