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

Int J Radiat Biol. 2000 Mar;76(3):391-402. doi: 10.1080/095530000138736.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Line
  • Collagen / biosynthesis
  • Collagen / genetics
  • Dose-Response Relationship, Radiation
  • Enzyme Activation / radiation effects
  • Epithelial Cells / cytology
  • Epithelial Cells / metabolism
  • Epithelial Cells / radiation effects*
  • Extracellular Matrix / metabolism*
  • Extracellular Matrix / radiation effects
  • Fibronectins / biosynthesis
  • Fibronectins / genetics
  • Gamma Rays
  • Gelatin / metabolism
  • Gene Expression Regulation / radiation effects*
  • Kidney Tubules / cytology
  • Kidney Tubules / metabolism
  • Kidney Tubules / radiation effects*
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / metabolism
  • Plasminogen Activator Inhibitor 1 / biosynthesis
  • Plasminogen Activator Inhibitor 1 / genetics
  • RNA, Messenger / biosynthesis
  • Rats
  • Tissue Inhibitor of Metalloproteinase-2 / biosynthesis
  • Tissue Inhibitor of Metalloproteinase-2 / genetics
  • Transforming Growth Factor beta / biosynthesis
  • Transforming Growth Factor beta / genetics
  • Up-Regulation / radiation effects


  • Fibronectins
  • Plasminogen Activator Inhibitor 1
  • RNA, Messenger
  • Transforming Growth Factor beta
  • Tissue Inhibitor of Metalloproteinase-2
  • Gelatin
  • Collagen
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9