Irradiation of rat tubule epithelial cells alters the expression of gene products associated with the synthesis and degradation of extracellular matrix

PURPOSE: To determine the ability of radiation to modulate kidney tubule epithelial cell expression of various molecules involved in regulating extracellular matrix accumulation (collagen types I and III, fibronectin, plasminogen activator-inhibitor 1 (PAI-1), TGF-beta and tissue inhibitor of metalloproteinases-2 (TIMP-2)) and degradation (plasminogen activators u-PA or t-PA, MMP-2 and MMP-9). MATERIALS AND METHODS: NRK52E rat tubule epithelial cells were placed in serum-free medium 24 h prior to irradiation with single doses of 1.0-10.0 Gy 137Cs gamma-rays. After irradiation, cells were maintained in serum-free medium for up to 48 h. RESULTS: Irradiation of NRK52E cells was associated with significant dose-dependent increases in collagen I (p<0.05) and PAI-1 (p< or =0.002) mRNA. Collagen III mRNA levels also exhibited a dose-dependent increase; however, this increase failed to reach levels that were statistically significant. Fibronectin mRNA levels were unaltered following irradiation. Radiation also led to an isoform-specific alteration in TGF-beta expression; TGF-beta1 mRNA increased, TGF-beta3 mRNA decreased. The amount of TGF-beta protein secreted into the medium was unchanged following irradiation; however, there was a fivefold increase in the relative amount of active TGF-beta. Irradiation was also associated with differential changes in MMP expression: active MMP-2 levels increased, while MMP-9 levels were unaltered; PA secretion into the medium was unchanged following irradiation. CONCLUSIONS: Irradiation of rat kidney tubule epithelial cells leads to altered production of various molecules associated with extracellular matrix accumulation and degradation.