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...
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Veröffentlicht in: | Experimental gerontology 2007-10, Vol.42 (10), p.1003-1011 |
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creator | Calabresi, Carmen Arosio, Beatrice Galimberti, Lorenza Scanziani, Eugenio Bergottini, Raffaella Annoni, Giorgio Vergani, Carlo |
description | 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. |
doi_str_mv | 10.1016/j.exger.2007.06.016 |
format | Article |
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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.</description><identifier>ISSN: 0531-5565</identifier><identifier>EISSN: 1873-6815</identifier><identifier>DOI: 10.1016/j.exger.2007.06.016</identifier><identifier>PMID: 17706388</identifier><language>eng</language><publisher>England: Elsevier Inc</publisher><subject>Aging ; Aging - genetics ; Aging - metabolism ; Animals ; Collagen ; Collagen - genetics ; Collagen - metabolism ; Extracellular Matrix - metabolism ; Fibronectins - metabolism ; Fibrosis ; Gene Expression Regulation ; Lung ; Lung - metabolism ; Male ; Matrix metalloproteinases ; Matrix Metalloproteinases - physiology ; Pulmonary Fibrosis - genetics ; Pulmonary Fibrosis - metabolism ; Rats ; Rats, Sprague-Dawley ; Reverse Transcriptase Polymerase Chain Reaction - methods ; RNA, Messenger - genetics ; Tissue Inhibitor of Metalloproteinases - metabolism</subject><ispartof>Experimental gerontology, 2007-10, Vol.42 (10), p.1003-1011</ispartof><rights>2007 Elsevier Inc.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c499t-23dc982b6fae68c40ae0a5b9a4cfb465bb46cd10d70d7acbde0cb73b7d5dd1a13</citedby><cites>FETCH-LOGICAL-c499t-23dc982b6fae68c40ae0a5b9a4cfb465bb46cd10d70d7acbde0cb73b7d5dd1a13</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.exger.2007.06.016$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17706388$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Calabresi, Carmen</creatorcontrib><creatorcontrib>Arosio, Beatrice</creatorcontrib><creatorcontrib>Galimberti, Lorenza</creatorcontrib><creatorcontrib>Scanziani, Eugenio</creatorcontrib><creatorcontrib>Bergottini, Raffaella</creatorcontrib><creatorcontrib>Annoni, Giorgio</creatorcontrib><creatorcontrib>Vergani, Carlo</creatorcontrib><title>Natural aging, expression of fibrosis-related genes and collagen deposition in rat lung</title><title>Experimental gerontology</title><addtitle>Exp Gerontol</addtitle><description>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.</description><subject>Aging</subject><subject>Aging - genetics</subject><subject>Aging - metabolism</subject><subject>Animals</subject><subject>Collagen</subject><subject>Collagen - genetics</subject><subject>Collagen - metabolism</subject><subject>Extracellular Matrix - metabolism</subject><subject>Fibronectins - metabolism</subject><subject>Fibrosis</subject><subject>Gene Expression Regulation</subject><subject>Lung</subject><subject>Lung - metabolism</subject><subject>Male</subject><subject>Matrix metalloproteinases</subject><subject>Matrix Metalloproteinases - physiology</subject><subject>Pulmonary Fibrosis - genetics</subject><subject>Pulmonary Fibrosis - metabolism</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Reverse Transcriptase Polymerase Chain Reaction - methods</subject><subject>RNA, Messenger - genetics</subject><subject>Tissue Inhibitor of Metalloproteinases - metabolism</subject><issn>0531-5565</issn><issn>1873-6815</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkE1r3DAQhkVp6G62_QWFoFNPtTOybMk-5FBCmwSW5JLQo9DH2Gjx2hvJLpt_H212IbcGhISG552RHkK-M8gZMHG5yXHfYcgLAJmDyFPtE1myWvJM1Kz6TJZQcZZVlagW5DzGDQCIgrMvZMGkBMHrekn-3utpDrqnuvND95PifhcwRj8OdGxp600Yo49ZwF5P6GiHA0aqB0ft2Pc6XanDXUKmQ8IPNOiJ9vPQfSVnre4jfjudK_L05_fj9W22fri5u_61zmzZNFNWcGebujCi1ShqW4JG0JVpdGlbU4rKpM06Bk6mpa1xCNZIbqSrnGOa8RX5cey7C-PzjHFSWx8tprcNOM5RiZozVjD5IZgs8gZEmUB-BG36egzYql3wWx1eFAN1EK826k38ISIVCJVqKXVxaj-bLbr3zMl0Aq6OACYb_3yKR-txsOh8QDspN_r_DngFsUSXLw</recordid><startdate>20071001</startdate><enddate>20071001</enddate><creator>Calabresi, Carmen</creator><creator>Arosio, Beatrice</creator><creator>Galimberti, Lorenza</creator><creator>Scanziani, Eugenio</creator><creator>Bergottini, Raffaella</creator><creator>Annoni, Giorgio</creator><creator>Vergani, Carlo</creator><general>Elsevier Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20071001</creationdate><title>Natural aging, expression of fibrosis-related genes and collagen deposition in rat lung</title><author>Calabresi, Carmen ; Arosio, Beatrice ; Galimberti, Lorenza ; Scanziani, Eugenio ; Bergottini, Raffaella ; Annoni, Giorgio ; Vergani, Carlo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c499t-23dc982b6fae68c40ae0a5b9a4cfb465bb46cd10d70d7acbde0cb73b7d5dd1a13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Aging</topic><topic>Aging - genetics</topic><topic>Aging - metabolism</topic><topic>Animals</topic><topic>Collagen</topic><topic>Collagen - genetics</topic><topic>Collagen - metabolism</topic><topic>Extracellular Matrix - metabolism</topic><topic>Fibronectins - metabolism</topic><topic>Fibrosis</topic><topic>Gene Expression Regulation</topic><topic>Lung</topic><topic>Lung - metabolism</topic><topic>Male</topic><topic>Matrix metalloproteinases</topic><topic>Matrix Metalloproteinases - physiology</topic><topic>Pulmonary Fibrosis - genetics</topic><topic>Pulmonary Fibrosis - metabolism</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Reverse Transcriptase Polymerase Chain Reaction - methods</topic><topic>RNA, Messenger - genetics</topic><topic>Tissue Inhibitor of Metalloproteinases - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Calabresi, Carmen</creatorcontrib><creatorcontrib>Arosio, Beatrice</creatorcontrib><creatorcontrib>Galimberti, Lorenza</creatorcontrib><creatorcontrib>Scanziani, Eugenio</creatorcontrib><creatorcontrib>Bergottini, Raffaella</creatorcontrib><creatorcontrib>Annoni, Giorgio</creatorcontrib><creatorcontrib>Vergani, Carlo</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Experimental gerontology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Calabresi, Carmen</au><au>Arosio, Beatrice</au><au>Galimberti, Lorenza</au><au>Scanziani, Eugenio</au><au>Bergottini, Raffaella</au><au>Annoni, Giorgio</au><au>Vergani, Carlo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Natural aging, expression of fibrosis-related genes and collagen deposition in rat lung</atitle><jtitle>Experimental gerontology</jtitle><addtitle>Exp Gerontol</addtitle><date>2007-10-01</date><risdate>2007</risdate><volume>42</volume><issue>10</issue><spage>1003</spage><epage>1011</epage><pages>1003-1011</pages><issn>0531-5565</issn><eissn>1873-6815</eissn><abstract>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.</abstract><cop>England</cop><pub>Elsevier Inc</pub><pmid>17706388</pmid><doi>10.1016/j.exger.2007.06.016</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Aging Aging - genetics Aging - metabolism Animals Collagen Collagen - genetics Collagen - metabolism Extracellular Matrix - metabolism Fibronectins - metabolism Fibrosis Gene Expression Regulation Lung Lung - metabolism Male Matrix metalloproteinases Matrix Metalloproteinases - physiology Pulmonary Fibrosis - genetics Pulmonary Fibrosis - metabolism Rats Rats, Sprague-Dawley Reverse Transcriptase Polymerase Chain Reaction - methods RNA, Messenger - genetics Tissue Inhibitor of Metalloproteinases - metabolism |
title | Natural aging, expression of fibrosis-related genes and collagen deposition in rat lung |
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