Age-related increase in expression of TGF-beta1 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. Transforming growth factor-beta1 (TGF-beta1) is known to play a critical role in the genesis of these alterations in pathologic conditions. The present experiments were designed to test the hypothesis that TGF-beta1 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 interstitial lesions. In this study, 3-, 18-, 24-, and 30-mo-old rats were examined, and an age-related increase in urinary protein excretion was found; plasma creatinine and systolic BP did not change. Significant structural changes, including glomerular sclerosis and interstitial fibrosis, were found in the group of aged rats (24- and 30-mo-old). Immunostaining for TGF-beta in the renal cortex interstitium was increased in the group of 24-mo-old rats, with a parallel increase in TGF-beta1 mRNA expression, measured with reverse-transcription PCR. Captopril-treated animals showed a statistically significant decrease in urinary protein excretion but no significant changes in BP. Moreover, captopril reduced the extent of interstitial fibrosis, but did not affect the degree of glomerulosclerosis. A significant inhibition of TGF-beta1 mRNA expression was observed in the captopril-treated animals. These findings suggest that TGF-beta1 may act as a fibrogenic growth factor that could be responsible, at least partially, for the renal interstitial fibrosis associated with aging. Treatment with captopril might delay the progression of these lesions.
Ruiz-Torres
M P
MP
Department of Physiology, Alcalá School of Medicine, University of Alcalá, Alcalá de Henares (Madrid), Spain.
Bosch
R J
RJ
O'Valle
F
F
Del Moral
R G
RG
Ramírez
C
C
Masseroli
M
M
Pérez-Caballero
C
C
Iglesias
M C
MC
Rodríguez-Puyol
M
M
Rodríguez-Puyol
D
D
D000375:Aging / Q000502:physiology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D002216:Captopril / Q000494:pharmacology; D007150:Immunohistochemistry; D007668:Kidney / Q000187:drug effects / Q000254:growth & development* / Q000378:metabolism*; D007672:Kidney Cortex / Q000187:drug effects / Q000473:pathology; D007678:Kidney Glomerulus / Q000187:drug effects / Q000473:pathology; D008297:Male; D016133:Polymerase Chain Reaction; D011507:Proteinuria / Q000652:urine; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014158:Transcription, Genetic; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*
D000806:Angiotensin-Converting Enzyme Inhibitors; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D002216:Captopril