ACE inhibitors attenuate expression of renal transforming growth factor-beta1 in humans.
Progressive nephropathies are characterized by the enhanced accumulation of extracellular matrix in the kidney. Overproduction of transforming growth factor-beta (TGF-beta) was shown to result in pathological tissue fibrosis through the accumulation of extracellular matrix proteins. It has been proposed that angiotensin II stimulates TGF-beta production. Despite accumulating data supporting the effects of angiotensin-converting enzyme (ACE) inhibitors on the attenuation of TGF-beta in vitro and in rats, such studies in humans are lacking. The present study sought to determine the effects of ACE inhibitors on TGF-beta1 in patients with glomerulonephritis. Using competitive polymerase chain reaction and the sandwich enzyme-linked immunosorbent assay, TGF-beta1 messenger RNA (mRNA) abundance and TGF-beta1 protein levels were measured. Patients with immunoglobulin A nephropathy administered ACE inhibitors showed significantly lower renal TGF-beta1 gene expression than patients not administered these medications (mean ratios of TGF-beta1/beta-actin, 4.27 +/- 0.62 [SEM] versus 14.81 +/- 3.87; P < 0.05), whereas no difference was noted between patients administered ACE inhibitors and healthy controls (4.27 +/- 0.62 versus 2.78 +/- 0.71). ACE inhibitor therapy did not affect TGF-beta1 mRNA expression in freshly isolated mononuclear cells. Urine and serum TGF-beta1 protein levels were not affected by the administration of ACE inhibitors. However, possibly a longer duration of treatment would decrease TGF-beta1 levels in urine or blood. In conclusion, we observed a significant reduction in 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.
Shin
G T
GT
Department of Nephrology, Ajou University School of Medicine, Suwon, South Korea. gtshin@madang.ajou.ac.kr
Kim
S J
SJ
Ma
K A
KA
Kim
H S
HS
Kim
D
D
D000293:Adolescent; D000328:Adult; D000368:Aged; D017311:Amlodipine / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000627:therapeutic use; D005260:Female; D005786:Gene Expression Regulation; D005921:Glomerulonephritis / Q000097:blood / Q000188:drug therapy* / Q000652:urine; D005922:Glomerulonephritis, IGA / Q000097:blood / Q000652:urine; D006801:Humans; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009543:Nifedipine / Q000494:pharmacology; D016133:Polymerase Chain Reaction / Q000379:methods; D012333:RNA, Messenger / Q000097:blood / Q000652:urine; D016212:Transforming Growth Factor beta / Q000097:blood / Q000187:drug effects* / Q000652:urine; D053773:Transforming Growth Factor beta1
D000806:Angiotensin-Converting Enzyme Inhibitors; D002121:Calcium Channel Blockers; D012333:RNA, Messenger; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D017311:Amlodipine; D009543:Nifedipine