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 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 factor beta-1 (TGFbeta-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.
Calabresi
Carmen
C
Department of Internal Medicine, Ospedale Maggiore IRCCS, University of Milan, Italy.
Arosio
Beatrice
B
Galimberti
Lorenza
L
Scanziani
Eugenio
E
Bergottini
Raffaella
R
Annoni
Giorgio
G
Vergani
Carlo
C
D000375:Aging / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D003094:Collagen / Q000235:genetics / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D005786:Gene Expression Regulation; D008168:Lung / Q000378:metabolism*; D008297:Male; D020782:Matrix Metalloproteinases / Q000502:physiology; D011658:Pulmonary Fibrosis / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism
D005353:Fibronectins; D012333:RNA, Messenger; D019714:Tissue Inhibitor of Metalloproteinases; D003094:Collagen; D020782:Matrix Metalloproteinases