Age-dependent expression of fibrosis-related genes and collagen deposition in 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 transforming growth factors beta1 and beta3 (TGF-beta1 and TGF-beta3)] of interstiti...

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Published in:The journals of gerontology. Series A, Biological sciences and medical sciences Biological sciences and medical sciences, 2000-08, Vol.55 (8), p.B365-B372
Main Authors: Gagliano, N, Arosio, B, Santambrogio, D, Balestrieri, M R, Padoani, G, Tagliabue, J, Masson, S, Vergani, C, Annoni, G
Format: Article
Language:English
Subjects:
Age Factors
Aging
Animals
Collagen - biosynthesis
Collagen - genetics
Fibrosis
Gene Expression
Genes
Gerontology
Hydroxyproline - metabolism
Kidney Cortex - enzymology
Kidney Cortex - metabolism
Kidney Cortex - pathology
Kidneys
Male
Matrix Metalloproteinase 1 - metabolism
Matrix Metalloproteinase 2 - metabolism
Rats
Rats, Sprague-Dawley
RNA, Messenger - biosynthesis
Rodents
Transforming Growth Factor beta - biosynthesis
Transforming Growth Factor beta - genetics
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Summary: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 transforming growth factors beta1 and beta3 (TGF-beta1 and TGF-beta3)] 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-beta in the renal cortex is not modified.
ISSN:1079-5006
1758-535X
DOI:10.1093/gerona/55.8.B365