AGE-RELATED INCREASE IN EXPRESSION OF TGF-BETA-1 IN THE RAT-KIDNEY - RELATIONSHIP TO MORPHOLOGIC CHANGES

In the kidney, aging is characterized by the development of structural changes, including glomerulosclerosis and interstitial fibrosis. Tran sforming growth factor-beta 1 (TGF-beta 1) is known to play a critical role in the genesis of these alterations in pathologic conditions. Th e present experiments were designed to test the hypothesis that TGF-be ta 1 may be involved in the development of age-related histopathologic changes in rat kidney, and that captopril, an angiotensin-converting enzyme inhibitor, may influence the progression of glomerular and inte rstitial lesions. In this study, 3-, 18-, 24-, and 30-mo-old rats were examined, and an age-related increase in urinary protein excretion wa s found; plasma creatinine and systolic BP did not change. Significant structural changes, including glomerular sclerosis and interstitial f ibrosis, were found in the group of aged rats (24- and 30-mo-old). Imm unostaining for TGF-beta in the renal cortex interstitium was increase d in the group of 24-mo-old rats, with a parallel increase in TGF-beta 1 mRNA expression, measured with reverse-transcription PCR. Captopril -treated animals showed a statistically significant decrease in urinar y protein excretion but no significant changes in BP. Moreover, captop ril reduced the extent of interstitial fibrosis, but did not affect th e degree of glomerulosclerosis. A significant inhibition of TGF-beta 1 mRNA expression was observed in the captopril-treated animals. These findings suggest that TGF-beta 1 may act as a fibrogenic growth factor that could be responsible, at least partially, for the renal intersti tial fibrosis associated with aging. Treatment with captopril might de lay the progression of these lesions.