Age-dependent expression of fibrosis-related genes and collagen depositionin rat kidney cortex

Because progressive fibrosis is a histological hallmark of the aging kidney , we sought to characterize the course of some fibrosis-related genes [pro- alpha2(I)collagen (COL-I), pro-alpha1(III)collagen (COL-III), and transform ing growth Factors beta1 and beta3 (TGF-beta1 and TGF-beta3)] of interstiti al collagen accumulation [COL-I and COL-III proteins, hydroxyproline (PRO-O H), histology] and its degradation (matrix metalloproteinase MMP-1 and -2) during maturation and early aging in rats. During the lifespan considered w e observed no changes in the mRNA, except that COL-I mRNA tended to be up-r egulated from 2 to 19 months of age. However, progressive fibrosis was hist ologically detectable, with COL-I accumulation (p <.05 and p <.01 in 12-mon th- and 19-month-old rats vs the youngest), and confirmed by the PRO-OH tis sue levels (p =.0001); COL-III seemed to be less involved. The MMP-1 protei n level decreased significantly in the cortex of 12-month- and 19-month-old rats (p <.05), whereas MMP-2 protein level and activity remained essential ly unchanged. These results show that, during aging of the kidney, (i) rena l cortex fibrosis is explained by COL-I accumulation as a consequence of an altered balance between its synthesis and degradation, and (ii) the expres sion of the pleiotropic factor TGF-<beta> in the renal cortex is not modifi ed.