The present study was performed to clarify the mechanism underlying the beneficial effects of
lisinopril on chronic
glomerulonephritis. Chronic
glomerulonephritis was induced by a single injection of E30
monoclonal antibody (E30) recognizing
Thy-1.1 antigen to unilaterally nephrectomized rats. E30 injection resulted in persistent massive
proteinuria with a decrease in anionic charge sites on the glomerular basement membrane (GBM) at 8 weeks. Also, renal tissue from rats treated with E30 showed typical glomerulosclerosis and tubulointerstitial
fibrosis.
Lisinopril exerted a potent antiproteinuric effect and suppressed the progression of both glomerulosclerosis and tubulointerstitial
fibrosis.
Lisinopril recovered the reduced number of anionic charge sites on GBM, accounting for the positive action against massive
proteinuria. Immunostaining for
desmin revealed that
lisinopril treatment prevented the injury of glomerular epithelial cells (GECs) occurring in the chronic nephritic stage. Also, the level of gene expression of
transforming growth factor-beta (
TGF-beta) and
plasminogen activator inhibitor-1 (PAI-1) in the renal cortex were reduced, suggesting that
lisinopril improved extracellular matrix (ECM) metabolism. These results indicated that
proteinuria in Thy-1.1 antibody-induced chronic
nephritis is associated with a decrease in anionic charge sites on GBM, and that the antiproteinuric effect of
lisinopril is attributable to protection against GEC damage. Suppression of
TGF-beta and
PAI-1 expression contributed to the preventive effect of
lisinopril on ECM deposition in renal tissue.