Changes in transforming growth factor-beta (TGF-beta 1), procollagen types I and II mRNA in the rat heart after irradiation.
OBJECTIVE
To study alteration in gene transcription (transforming growth factor-beta 1 and procollagen types I and III) involved in radiation-induced cardiac damage.


METHODS
Female Sprague-Dawley rats were irradiated with a single dose of 0, 15, 20 or 25 Gy locally on the heart. At intervals up to 16 months after irradiation, absolute amounts of mRNA were quantified using a (semi-nested) competitive PCR assay. All values were normalized to equal input cDNA with respect to their GAPDH content.


RESULTS
After irradiation, left ventricular TGF-beta 1 mRNA levels increased sharply. This response was bi-phasic with peaks at days 1 and 12 (maximum 6-fold baseline), then returning to control levels by 1 month. After 20 Gy, a persistent elevation was observed from 6 months, but this elevation was less profound (approximately 1.5-fold baseline) when compared with the early response (1-12 days). Absolute mRNA levels of procollagen type I hardly changed during the first 6 months, but thereafter these levels increased progressively until the end of observation. An age-related increase in procollagen I was also observed. Procollagen type III mRNA levels were increased between days 1 and 12, returned to control values and remained low up to 6 months, then mRNA levels rose again with increasing time post-treatment.


CONCLUSIONS
The difference in time-course between TGF-beta 1 and procollagen mRNA expression after local heart irradiation and ageing strongly suggest that the late up-regulation of both procollagen types in the left ventricle occurs without TGF-beta 1 over-expression.
Krüse
J J
JJ
LUMC, Department of Clinical Oncology, Leiden, The Netherlands. KRUSE_J@RULLF2.MEDFAC.LEIDENUNIV.NL
Bart
C I
CI
Visser
A
A
Wondergem
J
J
D000818:Animals; D009202:Cardiomyopathies / Q000235:genetics; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006321:Heart / Q000528:radiation effects*; D009206:Myocardium / Q000378:metabolism*; D011347:Procollagen / Q000096:biosynthesis* / Q000235:genetics / Q000528:radiation effects; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000378:metabolism / Q000528:radiation effects*; D011833:Radiation Injuries, Experimental / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D014158:Transcription, Genetic / Q000528:radiation effects; D016212:Transforming Growth Factor beta / Q000096:biosynthesis* / Q000235:genetics / Q000528:radiation effects; D016277:Ventricular Function, Left / Q000528:radiation effects
D011347:Procollagen; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta