Because progressive fibrosis is a histological hallmark of the aging kidney, we sought to characterize the course of some fibrosis-related genes [pro-α2(I)collagen (COL-I, pro-α1(III)collagen (COL-III), and transforming growth factors β1 and β3 (TGF-β1 and TGF-β3)] of interstitial collagen accumulation [COL-I and COL-III proteins, hydroxyproline (PRO-OH), histology] and its degradation (matrix metalloproteinase MMP-1 and -2) during maturation and early aging in rats. During the lifespan considered we observed no changes in the mRNA, except that COL-I mRNA tended to be up-regulated from 2 to 19 months of age. However, progressive fibrosis was histologically detectable, with COL-I accumulation (p <.05 and p <.01 in 12-month- and 19-month-old rats vs the youngest), and confirmed by the PRO-OH tissue levels (p = .0001); COL-III seemed to be less involved. The MMP-1 protein level decreased significantly in the cortex of 12-month- and 19-month-old rats (p <.05), whereas MMP-2 protein level and activity remained essentially unchanged. These results show that, during aging of the kidney, (i) renal cortex fibrosis is explained by COL-I accumulation as a consequence of an altered balance between its synthesis and degradation, and (ii) the expression of the pleiotropic factor TGF-β in the renal cortex is not modified.
|Journal||Journals of Gerontology - Series A Biological Sciences and Medical Sciences|
|Publication status||Published - 2000|
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