Korean J Nephrol.  2000 Jul;19(4):604-611.

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

• Kim SJ
• Shin GT
• Ma KA
• Kim HS
• Kim DH

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.

Keyword

Angiotensin II; ACE inhibitor; TGF-beta

MeSH Terms

Angiotensin II
Angiotensin-Converting Enzyme Inhibitors*
Angiotensins
Animals
Extracellular Matrix
Extracellular Matrix Proteins
Fibrosis
Gene Expression*
Glomerulonephritis
Glomerulonephritis, IGA*
Humans
Immunoglobulin A*
Kidney
Polymerase Chain Reaction
Rats
Renal Insufficiency, Chronic
RNA, Messenger
Transforming Growth Factor beta*
Transforming Growth Factor beta1
Tumor Necrosis Factor-alpha*
Angiotensin II
Angiotensin-Converting Enzyme Inhibitors
Angiotensins
Extracellular Matrix Proteins
Immunoglobulin A
RNA, Messenger
Transforming Growth Factor beta
Transforming Growth Factor beta1
Tumor Necrosis Factor-alpha