Although moderate fibrosis is a histological hallmark of the aging liver. the molecular mechanisms underlying this phenomenon are little known. Here we provide a comprehensive description of hepatic collagen expression and metabolism during natural aging in rats, Interstitial collagen accumulated significantly in the oldest animals, mainly in the periportal area (P < 0.05, 19- vs, 2-month-old rats). This was ascribed to COL-III protein deposition (P < 0.05 vs. 2-month-old rats), rather than COL-I. Conversely the transcription activity of COL-III gene decreased (P < 0.05) during the considered lifespan (2-19-months). whereas COL-I and transforming growth fator-beta1 (TGF-beta1) mRNA content was substantially unchanged. In the aged rats, hepatic matrix metalloproteinases (NIMP) activity (both MMP-1 and MMP-2) dropped significantly (P < 0.05). with a concomitant increase of the inactive tissue inhibitor of MNIP (TIMP-1)/MMP-1 complex (P < 0.05). MMP-2 and TIMP-1 levels were bleakly affected. All together, these results suggest that during natural aging, (i) COL III is the protein that accumulates preferentially in the liver: (ii) liver fibrosclerosis is mainly explained by a reduced proteolytic activity of matrix MMP in which TIMP-1 seems to be a major regulating factor

Gagliano, N., Arosio, B., Grizzi, F., Masson, S., Tagliabue, J., Dioguardi, N., et al. (2002). Reduced collagenolytic activity of matrix metalloproteinases and development of liver fibrosis in the aging rat. MECHANISMS OF AGEING AND DEVELOPMENT, 123(4), 413-425 [10.1016/S0047-6374(01)00398-0].

Reduced collagenolytic activity of matrix metalloproteinases and development of liver fibrosis in the aging rat

ANNONI, GIORGIO
2002

Abstract

Although moderate fibrosis is a histological hallmark of the aging liver. the molecular mechanisms underlying this phenomenon are little known. Here we provide a comprehensive description of hepatic collagen expression and metabolism during natural aging in rats, Interstitial collagen accumulated significantly in the oldest animals, mainly in the periportal area (P < 0.05, 19- vs, 2-month-old rats). This was ascribed to COL-III protein deposition (P < 0.05 vs. 2-month-old rats), rather than COL-I. Conversely the transcription activity of COL-III gene decreased (P < 0.05) during the considered lifespan (2-19-months). whereas COL-I and transforming growth fator-beta1 (TGF-beta1) mRNA content was substantially unchanged. In the aged rats, hepatic matrix metalloproteinases (NIMP) activity (both MMP-1 and MMP-2) dropped significantly (P < 0.05). with a concomitant increase of the inactive tissue inhibitor of MNIP (TIMP-1)/MMP-1 complex (P < 0.05). MMP-2 and TIMP-1 levels were bleakly affected. All together, these results suggest that during natural aging, (i) COL III is the protein that accumulates preferentially in the liver: (ii) liver fibrosclerosis is mainly explained by a reduced proteolytic activity of matrix MMP in which TIMP-1 seems to be a major regulating factor
Articolo in rivista - Articolo scientifico
liver; aging; fibrosis; matrix metalloproteinases
English
feb-2002
123
4
413
425
open
Gagliano, N., Arosio, B., Grizzi, F., Masson, S., Tagliabue, J., Dioguardi, N., et al. (2002). Reduced collagenolytic activity of matrix metalloproteinases and development of liver fibrosis in the aging rat. MECHANISMS OF AGEING AND DEVELOPMENT, 123(4), 413-425 [10.1016/S0047-6374(01)00398-0].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/730
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