Irradiation of rat mesangial cells alters the expression of gene products associated with the development of renal fibrosis.
To determine the ability of radiation to modulate mesangial cell expression of various molecules involved in promoting extracellular matrix (ECM) accumulation [fibronectin, plasminogen activator-inhibitor 1 (Pai1), and tissue inhibitor of metalloproteinase-2 (Timp2)] and degradation (Tgfb, plasminogen activators u-PA or t-PA, matrix metalloproteinases Mmp2 and Mmp9), primary cultures of rat mesangial cells (passage number 6-11) were placed in serum-free medium 24 h prior to irradiation with single doses of 0.5-20 Gy (137)Cs gamma rays. After irradiation, cells were maintained in serum-free medium for a further 48 h. Irradiation of quiescent mesangial cells resulted in significant (P < 0.05) time- and dose-dependent increases in Fn and Pai1 mRNA and/or immunoreactive protein. Despite an increase in Tgfb1 mRNA, there was little evidence for an increase in total Tgfb protein. Indeed, active levels remained unaltered after irradiation. Irradiation led to differential changes in MMP expression; active Mmp2 levels increased, while Mmp9 levels appeared unaltered. In addition, secretion of plasminogen activators into the medium was unchanged after irradiation, while secretion of Timp2 increased. We conclude that irradiating mesangial cells leads to altered production of various molecules involved in accumulation and degradation of extracellular matrix.
Radiation Research Laboratory, Department of Radiology, The University of Iowa, Iowa City, Iowa 52242, USA.
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W
Zhao
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Y
O'Malley
M E
ME
Robbins
D000818:Animals; D017364:Collagenases / Q000528:radiation effects; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D005353:Fibronectins / Q000235:genetics; D005355:Fibrosis; D018093:Gelatinases / Q000528:radiation effects; D005786:Gene Expression Regulation / Q000528:radiation effects*; D005920:Glomerular Mesangium / Q000378:metabolism / Q000528:radiation effects*; D008297:Male; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D008666:Metalloendopeptidases / Q000528:radiation effects; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000032:analysis / Q000528:radiation effects; D016212:Transforming Growth Factor beta / Q000235:genetics
D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D017395:Plasminogen Activator Inhibitor 1; D016212:Transforming Growth Factor beta; D019716:Tissue Inhibitor of Metalloproteinase-2; D017364:Collagenases; D018093:Gelatinases; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9