Changes in transforming growth factor-beta (TGF-beta1), procollagen types I and III mRNA in the rat heart after irradiation

Abstract

Purpose: To study alteration in gene transcription (transforming growth factor-beta1 and procollagen types I and III) involved in radiation-induced cardiac damage. Materials and methods: Female Sprague-Dawley rats were irradiated with a single dose of 0, 15, 20 or 25Gy 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-beta1 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 20Gy, a persistent elevation was observed from 6 months, but this elevation was less profound (~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 timepost-treatment. Conclusion: The difference in time-course between TGF-beta1 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-beta1 over-expression.