Natural aging, expression of fibrosis-related genes and collagen deposition in rat lung
Aging lung is characterized by morpho-structural modifications, including progressive fibrosis, that lead to an altered function. Here we provide a comprehensive description of lung collagen expression and metabolism during natural aging of rats. Peribronchial collagen increased significantly in the...
Gespeichert in:
Veröffentlicht in: | Experimental gerontology 2007-10, Vol.42 (10), p.1003-1011 |
---|---|
Hauptverfasser: | , , , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
Zusammenfassung: | Aging lung is characterized by morpho-structural modifications, including progressive fibrosis, that lead to an altered function. Here we provide a comprehensive description of lung collagen expression and metabolism during natural aging of rats. Peribronchial collagen increased significantly in the oldest animals (
p
=
0.05 2- vs. 6- and 19-month-old rats), as a consequence of Collagen-I and Collagen-III (COL-I, COL-III) protein accumulation (
p
<
0.05 in 6-, 12- and 19-month-old rats versus the youngest). No changes in fibronectin (FN) protein expression and in COL-III and transforming grow factorβ-1 (
TGFβ-1) mRNA expression were observed. Conversely the transcription activity of the
COL-I gene was overexpressed in the oldest animals (
p
<
0.05).
In the aged rats, the activity of lung matrix metalloproteinases (MMP), MMP-1 and MMP-2, dropped significantly (
p
<
0.05), whilst MMP-9 levels were slightly decreased. These changes were associated with a concomitant increase of tissue inhibitors of MMP (TIMP-1 and TIMP-2).
All together, these results suggest that, during natural aging, collagen accumulation in the lung and its progressive fibrosis are mainly due to a reduced proteolytic activity of MMP, in which TIMP-1 and -2 seem to be the major regulating factors. |
---|---|
ISSN: | 0531-5565 1873-6815 |
DOI: | 10.1016/j.exger.2007.06.016 |