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 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.
Gagliano
N
N
Department of Internal Medicine and Geriatrics, Milan and Milan-Bicocca University, Ospedale Maggiore Istituto di Ricovero e Cura a Carattere Scientifico, Italy.
Arosio
B
B
Santambrogio
D
D
Balestrieri
M R
MR
Padoani
G
G
Tagliabue
J
J
Masson
S
S
Vergani
C
C
Annoni
G
G
D000367:Age Factors; D000818:Animals; D003094:Collagen / Q000096:biosynthesis* / Q000235:genetics*; D005355:Fibrosis; D015870:Gene Expression; D006909:Hydroxyproline / Q000378:metabolism; D007672:Kidney Cortex / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D016212:Transforming Growth Factor beta / Q000096:biosynthesis* / Q000235:genetics*
D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D003094:Collagen; D020778:Matrix Metalloproteinase 2; D020781:Matrix Metalloproteinase 1; D006909:Hydroxyproline