The Effect of ACE Inhibitors on The Gene Expression of TGF-β and TNF- α in Renal Tissues from Patients with IgA Nephropathy

Abstract

Progressive nephropathies are characterized by the enhanced accumulation of extracellular matrix in the kidney. Overproduction of transforming growth factor .8 (TGF- l3) was shown to result in pathological fibrosis of tissue via the accumulation of extracellular matrix proteins. It has been proposed that angiotensin 11 stimulates the production of TGF-.8. Despite accumulating volume of data supporting the effects of angiotensin converting enzyme (ACE) inhibitors in the attenuation of TGF-18 in vitro and in rats, studies . in humans are absolutely lacking. There is ´evidence that TNF- a expression is increased in various glomerulonephritis. The present study sought to determine the effects of ACE inhibitors on TGF- .8 1 and TNF- a in patients with IgA nephropathy. Using competitive polymerase chain reaction, TGF- R 1 and TNFa mRNA abundance were measured. Patients taking ACE inhibitors showed significantly lower renal TGF.81 gene expression compared with patients not on these medications (ratios of TGF-.81/Q-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 (427±0.62 versus 2.78±0.71). ACE inhibitor therapy did not affect the TNF- a mRNA expression in renal tissue. In conclusion, we observed a significant reduction of the TGF-Q 1 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.