Renal transplant fibrosis correlates with intragraft expression of tissue inhibitor of metalloproteinase messenger RNA
Background: Chronic renal allograft nephropathy is characterized by an abnormal accumulation of extracellular matrix proteins in the glomeruli and tubulo‐interstitium. The aim of this study was to determine the relationship between intragraft expression of the genes controlling the accumulation of e...
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| Veröffentlicht in: | British journal of surgery 2002-07, Vol.89 (7), p.933-937 |
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| creator | Nicholson, M. L. Waller, J. R. Bicknell, G. R. |
| description | Background:
Chronic renal allograft nephropathy is characterized by an abnormal accumulation of extracellular matrix proteins in the glomeruli and tubulo‐interstitium. The aim of this study was to determine the relationship between intragraft expression of the genes controlling the accumulation of extracellular matrix and the development of chronic renal allograft nephropathy in human renal transplants.
Methods:
Forty renal allografts with stable renal function were biopsied 6 months after transplantation. Single glomeruli were plucked from the surface of these protocol biopsies and total messenger RNA (mRNA) was extracted. Reverse transcriptase–polymerase chain reaction was used to study the intragraft expression of several fibrosis‐associated genes (collagen III, collagen IVα2, matrix metalloproteinase (MMP) 2, tissue inhibitors of metalloproteinases (TIMPs) 1 and 2, tenascin and transforming growth factor (TGF) β). The level of tubulo‐interstitial fibrosis was measured by quantitative immunostaining of collagen III.
Results:
There were positive correlations between the level of tubulo‐interstitial collagen III immunostaining and intragraft expression of the genes for TIMP‐1 (r
S
= 0·70, P < 0·02) and TIMP‐2 (r
S
= 0·59, P < 0·02). Interstitial fibrosis was also strongly correlated with the levels of TGF‐β mRNA (r
S
= 0·67, P < 0·002). Finally, TIMP‐1 expression increased with TGF‐β expression (r
S
= 0·77, P < 0·002).
Conclusion:
Failure of extracellular matrix degradation may be an important molecular mechanism in the pathogenesis of chronic renal allograft damage. © 2002 British Journal of Surgery Society Ltd |
| doi_str_mv | 10.1046/j.1365-2168.2002.02118.x |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_proquest_miscellaneous_71847950</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>71847950</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4328-5fd65bc1626f451758b779052d0ca1bd7d1a394dd24abb5b55639e76888178bc3</originalsourceid><addsrcrecordid>eNpFkUtv1DAUhS0EokPhLyBvYJfgR_yIWJUK2qJqkAqoEhvLTpzWgyeZ-nro9N_jMEO7snTPd2yfexDClNSUNPLDqqZciopRqWtGCKsJo1TXu2do8Sg8RwtCiKooZ_wIvQJYEUI5EewlOqKMaKoauUB_rvxoI87JjrCJdsx4CC5NEAB3U0o-2uwB34d8i8NYqJtkh4z9bpM8QJhGPA04B4CtL_ptcCFPaZ6tfbYxTps0ZR9GC75MAPx44xO-Wp68Ri8GG8G_OZzH6OeXzz9Oz6vLb2cXpyeXVddwpisx9FK4jkomh0ZQJbRTqi0ZetJZ6nrVU8vbpu9ZY50TTgjJW6-k1iWedh0_Ru_395aP3G09ZLMO0PlYkvppC0ZR3ahWkAK-PYBbt_a92aSwtunB_N9UAd4dAAudjUNZWBfgieNKiIbwwn3cc_ch-ocnnZi5ObMyc0FmLsjMzZl_zZmd-fT1O9XFXe3dAbLfPbpt-m2kKk-Y6-WZkUuml9etNr_4XxpqnIw</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>71847950</pqid></control><display><type>article</type><title>Renal transplant fibrosis correlates with intragraft expression of tissue inhibitor of metalloproteinase messenger RNA</title><source>MEDLINE</source><source>Wiley Online Library Journals Frontfile Complete</source><source>Oxford University Press Journals All Titles (1996-Current)</source><creator>Nicholson, M. L. ; Waller, J. R. ; Bicknell, G. R.</creator><creatorcontrib>Nicholson, M. L. ; Waller, J. R. ; Bicknell, G. R.</creatorcontrib><description>Background:
Chronic renal allograft nephropathy is characterized by an abnormal accumulation of extracellular matrix proteins in the glomeruli and tubulo‐interstitium. The aim of this study was to determine the relationship between intragraft expression of the genes controlling the accumulation of extracellular matrix and the development of chronic renal allograft nephropathy in human renal transplants.
Methods:
Forty renal allografts with stable renal function were biopsied 6 months after transplantation. Single glomeruli were plucked from the surface of these protocol biopsies and total messenger RNA (mRNA) was extracted. Reverse transcriptase–polymerase chain reaction was used to study the intragraft expression of several fibrosis‐associated genes (collagen III, collagen IVα2, matrix metalloproteinase (MMP) 2, tissue inhibitors of metalloproteinases (TIMPs) 1 and 2, tenascin and transforming growth factor (TGF) β). The level of tubulo‐interstitial fibrosis was measured by quantitative immunostaining of collagen III.
Results:
There were positive correlations between the level of tubulo‐interstitial collagen III immunostaining and intragraft expression of the genes for TIMP‐1 (r
S
= 0·70, P < 0·02) and TIMP‐2 (r
S
= 0·59, P < 0·02). Interstitial fibrosis was also strongly correlated with the levels of TGF‐β mRNA (r
S
= 0·67, P < 0·002). Finally, TIMP‐1 expression increased with TGF‐β expression (r
S
= 0·77, P < 0·002).
Conclusion:
Failure of extracellular matrix degradation may be an important molecular mechanism in the pathogenesis of chronic renal allograft damage. © 2002 British Journal of Surgery Society Ltd</description><identifier>ISSN: 0007-1323</identifier><identifier>EISSN: 1365-2168</identifier><identifier>DOI: 10.1046/j.1365-2168.2002.02118.x</identifier><identifier>PMID: 12081746</identifier><identifier>CODEN: BJSUAM</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Science Ltd</publisher><subject>Biological and medical sciences ; Biopsy, Needle ; Female ; Fibrosis - metabolism ; Humans ; Immunohistochemistry - methods ; Kidney Diseases - metabolism ; Kidney Diseases - pathology ; Kidney Transplantation ; Kidneys ; Male ; Matrix Metalloproteinases - metabolism ; Medical sciences ; Middle Aged ; Nephrology. Urinary tract diseases ; Postoperative Complications - metabolism ; Postoperative Complications - pathology ; Reverse Transcriptase Polymerase Chain Reaction ; RNA, Messenger - metabolism ; Tissue Inhibitor of Metalloproteinase-1 - metabolism ; Tissue Inhibitor of Metalloproteinase-2 - metabolism ; Tissue Inhibitor of Metalloproteinases - metabolism ; Transplantation, Homologous ; Urinary system involvement in other diseases. Miscellaneous</subject><ispartof>British journal of surgery, 2002-07, Vol.89 (7), p.933-937</ispartof><rights>2002 British Journal of Surgery Society Ltd</rights><rights>2002 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4328-5fd65bc1626f451758b779052d0ca1bd7d1a394dd24abb5b55639e76888178bc3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1046%2Fj.1365-2168.2002.02118.x$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1046%2Fj.1365-2168.2002.02118.x$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1416,27915,27916,45565,45566</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=13755403$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12081746$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Nicholson, M. L.</creatorcontrib><creatorcontrib>Waller, J. R.</creatorcontrib><creatorcontrib>Bicknell, G. R.</creatorcontrib><title>Renal transplant fibrosis correlates with intragraft expression of tissue inhibitor of metalloproteinase messenger RNA</title><title>British journal of surgery</title><addtitle>Br J Surg</addtitle><description>Background:
Chronic renal allograft nephropathy is characterized by an abnormal accumulation of extracellular matrix proteins in the glomeruli and tubulo‐interstitium. The aim of this study was to determine the relationship between intragraft expression of the genes controlling the accumulation of extracellular matrix and the development of chronic renal allograft nephropathy in human renal transplants.
Methods:
Forty renal allografts with stable renal function were biopsied 6 months after transplantation. Single glomeruli were plucked from the surface of these protocol biopsies and total messenger RNA (mRNA) was extracted. Reverse transcriptase–polymerase chain reaction was used to study the intragraft expression of several fibrosis‐associated genes (collagen III, collagen IVα2, matrix metalloproteinase (MMP) 2, tissue inhibitors of metalloproteinases (TIMPs) 1 and 2, tenascin and transforming growth factor (TGF) β). The level of tubulo‐interstitial fibrosis was measured by quantitative immunostaining of collagen III.
Results:
There were positive correlations between the level of tubulo‐interstitial collagen III immunostaining and intragraft expression of the genes for TIMP‐1 (r
S
= 0·70, P < 0·02) and TIMP‐2 (r
S
= 0·59, P < 0·02). Interstitial fibrosis was also strongly correlated with the levels of TGF‐β mRNA (r
S
= 0·67, P < 0·002). Finally, TIMP‐1 expression increased with TGF‐β expression (r
S
= 0·77, P < 0·002).
Conclusion:
Failure of extracellular matrix degradation may be an important molecular mechanism in the pathogenesis of chronic renal allograft damage. © 2002 British Journal of Surgery Society Ltd</description><subject>Biological and medical sciences</subject><subject>Biopsy, Needle</subject><subject>Female</subject><subject>Fibrosis - metabolism</subject><subject>Humans</subject><subject>Immunohistochemistry - methods</subject><subject>Kidney Diseases - metabolism</subject><subject>Kidney Diseases - pathology</subject><subject>Kidney Transplantation</subject><subject>Kidneys</subject><subject>Male</subject><subject>Matrix Metalloproteinases - metabolism</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Nephrology. Urinary tract diseases</subject><subject>Postoperative Complications - metabolism</subject><subject>Postoperative Complications - pathology</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>RNA, Messenger - metabolism</subject><subject>Tissue Inhibitor of Metalloproteinase-1 - metabolism</subject><subject>Tissue Inhibitor of Metalloproteinase-2 - metabolism</subject><subject>Tissue Inhibitor of Metalloproteinases - metabolism</subject><subject>Transplantation, Homologous</subject><subject>Urinary system involvement in other diseases. Miscellaneous</subject><issn>0007-1323</issn><issn>1365-2168</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkUtv1DAUhS0EokPhLyBvYJfgR_yIWJUK2qJqkAqoEhvLTpzWgyeZ-nro9N_jMEO7snTPd2yfexDClNSUNPLDqqZciopRqWtGCKsJo1TXu2do8Sg8RwtCiKooZ_wIvQJYEUI5EewlOqKMaKoauUB_rvxoI87JjrCJdsx4CC5NEAB3U0o-2uwB34d8i8NYqJtkh4z9bpM8QJhGPA04B4CtL_ptcCFPaZ6tfbYxTps0ZR9GC75MAPx44xO-Wp68Ri8GG8G_OZzH6OeXzz9Oz6vLb2cXpyeXVddwpisx9FK4jkomh0ZQJbRTqi0ZetJZ6nrVU8vbpu9ZY50TTgjJW6-k1iWedh0_Ru_395aP3G09ZLMO0PlYkvppC0ZR3ahWkAK-PYBbt_a92aSwtunB_N9UAd4dAAudjUNZWBfgieNKiIbwwn3cc_ch-ocnnZi5ObMyc0FmLsjMzZl_zZmd-fT1O9XFXe3dAbLfPbpt-m2kKk-Y6-WZkUuml9etNr_4XxpqnIw</recordid><startdate>200207</startdate><enddate>200207</enddate><creator>Nicholson, M. L.</creator><creator>Waller, J. R.</creator><creator>Bicknell, G. R.</creator><general>Blackwell Science Ltd</general><general>Wiley</general><scope>BSCLL</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope></search><sort><creationdate>200207</creationdate><title>Renal transplant fibrosis correlates with intragraft expression of tissue inhibitor of metalloproteinase messenger RNA</title><author>Nicholson, M. L. ; Waller, J. R. ; Bicknell, G. R.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4328-5fd65bc1626f451758b779052d0ca1bd7d1a394dd24abb5b55639e76888178bc3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2002</creationdate><topic>Biological and medical sciences</topic><topic>Biopsy, Needle</topic><topic>Female</topic><topic>Fibrosis - metabolism</topic><topic>Humans</topic><topic>Immunohistochemistry - methods</topic><topic>Kidney Diseases - metabolism</topic><topic>Kidney Diseases - pathology</topic><topic>Kidney Transplantation</topic><topic>Kidneys</topic><topic>Male</topic><topic>Matrix Metalloproteinases - metabolism</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Nephrology. Urinary tract diseases</topic><topic>Postoperative Complications - metabolism</topic><topic>Postoperative Complications - pathology</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>RNA, Messenger - metabolism</topic><topic>Tissue Inhibitor of Metalloproteinase-1 - metabolism</topic><topic>Tissue Inhibitor of Metalloproteinase-2 - metabolism</topic><topic>Tissue Inhibitor of Metalloproteinases - metabolism</topic><topic>Transplantation, Homologous</topic><topic>Urinary system involvement in other diseases. Miscellaneous</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Nicholson, M. L.</creatorcontrib><creatorcontrib>Waller, J. R.</creatorcontrib><creatorcontrib>Bicknell, G. R.</creatorcontrib><collection>Istex</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><jtitle>British journal of surgery</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Nicholson, M. L.</au><au>Waller, J. R.</au><au>Bicknell, G. R.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Renal transplant fibrosis correlates with intragraft expression of tissue inhibitor of metalloproteinase messenger RNA</atitle><jtitle>British journal of surgery</jtitle><addtitle>Br J Surg</addtitle><date>2002-07</date><risdate>2002</risdate><volume>89</volume><issue>7</issue><spage>933</spage><epage>937</epage><pages>933-937</pages><issn>0007-1323</issn><eissn>1365-2168</eissn><coden>BJSUAM</coden><abstract>Background:
Chronic renal allograft nephropathy is characterized by an abnormal accumulation of extracellular matrix proteins in the glomeruli and tubulo‐interstitium. The aim of this study was to determine the relationship between intragraft expression of the genes controlling the accumulation of extracellular matrix and the development of chronic renal allograft nephropathy in human renal transplants.
Methods:
Forty renal allografts with stable renal function were biopsied 6 months after transplantation. Single glomeruli were plucked from the surface of these protocol biopsies and total messenger RNA (mRNA) was extracted. Reverse transcriptase–polymerase chain reaction was used to study the intragraft expression of several fibrosis‐associated genes (collagen III, collagen IVα2, matrix metalloproteinase (MMP) 2, tissue inhibitors of metalloproteinases (TIMPs) 1 and 2, tenascin and transforming growth factor (TGF) β). The level of tubulo‐interstitial fibrosis was measured by quantitative immunostaining of collagen III.
Results:
There were positive correlations between the level of tubulo‐interstitial collagen III immunostaining and intragraft expression of the genes for TIMP‐1 (r
S
= 0·70, P < 0·02) and TIMP‐2 (r
S
= 0·59, P < 0·02). Interstitial fibrosis was also strongly correlated with the levels of TGF‐β mRNA (r
S
= 0·67, P < 0·002). Finally, TIMP‐1 expression increased with TGF‐β expression (r
S
= 0·77, P < 0·002).
Conclusion:
Failure of extracellular matrix degradation may be an important molecular mechanism in the pathogenesis of chronic renal allograft damage. © 2002 British Journal of Surgery Society Ltd</abstract><cop>Oxford, UK</cop><pub>Blackwell Science Ltd</pub><pmid>12081746</pmid><doi>10.1046/j.1365-2168.2002.02118.x</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | British journal of surgery, 2002-07, Vol.89 (7), p.933-937 |
| issn | 0007-1323 1365-2168 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_71847950 |
| source | MEDLINE; Wiley Online Library Journals Frontfile Complete; Oxford University Press Journals All Titles (1996-Current) |
| subjects | Biological and medical sciences Biopsy, Needle Female Fibrosis - metabolism Humans Immunohistochemistry - methods Kidney Diseases - metabolism Kidney Diseases - pathology Kidney Transplantation Kidneys Male Matrix Metalloproteinases - metabolism Medical sciences Middle Aged Nephrology. Urinary tract diseases Postoperative Complications - metabolism Postoperative Complications - pathology Reverse Transcriptase Polymerase Chain Reaction RNA, Messenger - metabolism Tissue Inhibitor of Metalloproteinase-1 - metabolism Tissue Inhibitor of Metalloproteinase-2 - metabolism Tissue Inhibitor of Metalloproteinases - metabolism Transplantation, Homologous Urinary system involvement in other diseases. Miscellaneous |
| title | Renal transplant fibrosis correlates with intragraft expression of tissue inhibitor of metalloproteinase messenger RNA |
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