The Effect of ACE Inhibitors on The Gene Expression of TGF-beta and TNF-alpha in Renal Tissues from Patients with IgA Nephropathy / 대한신장학회잡지

ABSTRACT

Progressive nephropathies are characterized by the enhanced accmulation of extracellular matrix in the kidney. Overproduction of transforming growth factor-beta(TGF-beta) was shown to result in pathological fibrosis of tissue via the accumulation of extracellular matrix proteins. It has been proposed that angiotensin II stimulates the production of TGF-beta. Despite accumulating volume of data supporting the effects of angiotensin converting enzyme(ACE) inhibitors in the attenuation of TGF-beta in vitro and in rats, studies in humans are absolutely lacking. There is evidence that TNF-alpha expression is increased in various glomerulonephritis. The present study sought to determine the effects of ACE inhibitors on TGF-beta1 and TNF-alpha in patients with IgA nephropathy. Using competitive polymerase chain reaction, TGF-beta1 and TNF-alpha mRNA abundance were measured. Patients taking ACE inhibitors showed significantly lower renal TGF-beta1 gene expression compared with patients not on these medications(ratios of TGF-beta1/beta-actin, 4.27+/-0.62 versus 14.81+/-3.87, p<0.05), whereas no difference was noted between patients on ACE inhibitors and normal controls(4.27+/-0.62 versus 2.78+/-0.71). ACE inhibitor therapy did not affect the TNF-alpha mRNA expres- sion in renal tissue. In conclusion, we observed a significant reduction of the TGF-beta1 expression in the kidney by ACE inhibitors, and this suggests that the effects of ACE inhibitors observed in animals can be extrapolated to patients with chronic renal disease.