Life-long dietary restriction modulates the expression of collagens and collagen-binding heat shock protein 47 in aged Fischer 344 rat kidney

It has been shown that the expression of HSP47 and collagens is substantial ly increased in the sclerotic/fibrotic process in various organs, including kidney. However, the factors regulating the increased expression of HSP47 are not yet clear. In this study, we examined the effect of dietary restric tion for the expression of collagens and collagen-binding HSP47 in the kidn eys of 6- and 24-month-old male Fischer 344 (F 344) rats fed ad libitum or 30% diet-restricted. No significant histological alteration was found in th e kidneys of 6-month-old fed or diet-restricted rats. Kidneys obtained from 24-month-old freely fed rats showed glomerulosclerosis with marked tubuloi nterstitial damage including interstitial fibrosis, while in the kidneys of 24-month-old diet-restricted rats, renal damage was remarkably less than t hose noted in 24-month-old freely fed rat kidneys. Immunohistochemical anal ysis showed an increased accumulation of type I, type III and type IV colla gens in areas of glomerulosclerosis and interstitial fibrosis in old rat ki dneys. Dietary restriction significantly reduces renal accumulation of coll agens in old age. Aging enhanced expression of HSP47 in 24-month-old freely fed rat kidneys whereas dietary restriction suppressed its expression in 2 4-month-old diet-restricted rat kidneys. Also, phenotypic alterations of me sangial cells and interstitial cells (immunopositive for alpha-smooth muscl e actin), glomerular epithelial cells (immunopositive for desmin) and tubul ar epithelial cells (immunopositive for vimentin) were seen in 24-month-old freely fed rat kidneys and found to express HSP47. Dietary restriction sig nificantly diminished phenotypically altered renal cells in 24-month-old ra t kidneys. Our results suggest that increased expression of HSP47 is associ ated with age-related renal damage and that diet-restricted alteration of i ts expression is associated with the modulation of age-associated renal scl erosis/fibrosis.