Pathogenesis of interstitial fibrosis in chronic purine aminonucleoside nephrosis
Pathogenesis of interstitial fibrosis in chronic purine aminonucleoside nephrosis. A cellular and molecular approach was used to gain new insight into the pathogenesis of interstitial fibrosis in chronic purine aminonucleoside nephrosis (PAN) nephrosis. Thirty experimental rats (PAN rats) were given...
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Veröffentlicht in: | Kidney international 1991-12, Vol.40 (6), p.1020-1031 |
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description | Pathogenesis of interstitial fibrosis in chronic purine aminonucleoside nephrosis. A cellular and molecular approach was used to gain new insight into the pathogenesis of interstitial fibrosis in chronic purine aminonucleoside nephrosis (PAN) nephrosis. Thirty experimental rats (PAN rats) were given 15 mg/100 g body wt of i.p. PAN at time 0, followed by 4.3 mg/100 g body wt i.p. on days 20, 27 and 34; 25 control rats received i.p. saline at the same time intervals. All rats had a right unilateral nephrectomy within the first four days. Groups of control and PAN rats were killed at 21, 37, 52, 72 and 91 days. Renal sections were studied by immunofluorescence to quantitate interstitial macrophages, T lymphocytes and fibroblasts, and to characterize the deposition of the extracellular matrix (ECM) proteins (collagens I, III and IV, fibronectin and laminin) and the tissue inhibitor of the metalloproteinases (TIMP). Steady state concentrations of mRNA from the whole kidney for these ECM proteins, the metalloproteinases, TIMP, and transforming growth factor beta (TGF-β1) were quantitated by Northern blot analysis. Significant increases in the number of interstitial macrophages and T lymphocytes were found in the PAN rat groups compared to that in controls. All ECM proteins examined were quantitatively increased in the tubulointerstitium of PAN rats. The pattern of distribution of some ECM proteins was also modified in experimental animals. TIMP was increased in the interstitium of PAN rats; at later times, TIMP was most prominent in sclerotic regions of the glomeruli and in tubular protein droplets. Northern blot analysis revealed increased steady-state mRNA levels for components of each of the ECM proteins, no change for the metalloproteinases—stromelysin or collagenase—and a marked increase for TIMP and TGF-β1 in PAN animals. The results of this study suggest that the diffuse interstitial fibrosis found in chronic PAN nephrosis results from both increased production of ECM proteins and decreased matrix degradation. |
doi_str_mv | 10.1038/ki.1991.310 |
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A cellular and molecular approach was used to gain new insight into the pathogenesis of interstitial fibrosis in chronic purine aminonucleoside nephrosis (PAN) nephrosis. Thirty experimental rats (PAN rats) were given 15 mg/100 g body wt of i.p. PAN at time 0, followed by 4.3 mg/100 g body wt i.p. on days 20, 27 and 34; 25 control rats received i.p. saline at the same time intervals. All rats had a right unilateral nephrectomy within the first four days. Groups of control and PAN rats were killed at 21, 37, 52, 72 and 91 days. Renal sections were studied by immunofluorescence to quantitate interstitial macrophages, T lymphocytes and fibroblasts, and to characterize the deposition of the extracellular matrix (ECM) proteins (collagens I, III and IV, fibronectin and laminin) and the tissue inhibitor of the metalloproteinases (TIMP). Steady state concentrations of mRNA from the whole kidney for these ECM proteins, the metalloproteinases, TIMP, and transforming growth factor beta (TGF-β1) were quantitated by Northern blot analysis. Significant increases in the number of interstitial macrophages and T lymphocytes were found in the PAN rat groups compared to that in controls. All ECM proteins examined were quantitatively increased in the tubulointerstitium of PAN rats. The pattern of distribution of some ECM proteins was also modified in experimental animals. TIMP was increased in the interstitium of PAN rats; at later times, TIMP was most prominent in sclerotic regions of the glomeruli and in tubular protein droplets. Northern blot analysis revealed increased steady-state mRNA levels for components of each of the ECM proteins, no change for the metalloproteinases—stromelysin or collagenase—and a marked increase for TIMP and TGF-β1 in PAN animals. The results of this study suggest that the diffuse interstitial fibrosis found in chronic PAN nephrosis results from both increased production of ECM proteins and decreased matrix degradation.</description><identifier>ISSN: 0085-2538</identifier><identifier>EISSN: 1523-1755</identifier><identifier>DOI: 10.1038/ki.1991.310</identifier><identifier>PMID: 1762303</identifier><identifier>CODEN: KDYIA5</identifier><language>eng</language><publisher>New York, NY: Elsevier Inc</publisher><subject>Albuminuria - etiology ; Animals ; Biological and medical sciences ; Chronic Disease ; Creatinine - blood ; Disease Models, Animal ; Extracellular Matrix Proteins - genetics ; Extracellular Matrix Proteins - metabolism ; Female ; Fibrosis ; Gene Expression ; Glycoproteins - genetics ; Glycoproteins - metabolism ; Interstitial nephritis ; Macrophages - metabolism ; Macrophages - pathology ; Medical sciences ; Metalloendopeptidases - antagonists & inhibitors ; Metalloendopeptidases - genetics ; Nephrology. Urinary tract diseases ; Nephropathies. Renovascular diseases. Renal failure ; Nephrosis - etiology ; Nephrosis - metabolism ; Nephrosis - pathology ; Puromycin Aminonucleoside ; Rats ; Rats, Inbred Lew ; Tissue Inhibitor of Metalloproteinases ; Transforming Growth Factor beta - genetics</subject><ispartof>Kidney international, 1991-12, Vol.40 (6), p.1020-1031</ispartof><rights>1991 International Society of Nephrology</rights><rights>1992 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c486t-ef6c5c8a0785eb966f48b5912b4661549ad4c8f3f06650148ace9c4df5e7e1d3</citedby><cites>FETCH-LOGICAL-c486t-ef6c5c8a0785eb966f48b5912b4661549ad4c8f3f06650148ace9c4df5e7e1d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=5095235$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/1762303$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Jones, Colin L.</creatorcontrib><creatorcontrib>Buch, Shilpa</creatorcontrib><creatorcontrib>Post, Martin</creatorcontrib><creatorcontrib>McCulloch, Lori</creatorcontrib><creatorcontrib>Liu, Elaine</creatorcontrib><creatorcontrib>Eddy, Allison A.</creatorcontrib><title>Pathogenesis of interstitial fibrosis in chronic purine aminonucleoside nephrosis</title><title>Kidney international</title><addtitle>Kidney Int</addtitle><description>Pathogenesis of interstitial fibrosis in chronic purine aminonucleoside nephrosis. A cellular and molecular approach was used to gain new insight into the pathogenesis of interstitial fibrosis in chronic purine aminonucleoside nephrosis (PAN) nephrosis. Thirty experimental rats (PAN rats) were given 15 mg/100 g body wt of i.p. PAN at time 0, followed by 4.3 mg/100 g body wt i.p. on days 20, 27 and 34; 25 control rats received i.p. saline at the same time intervals. All rats had a right unilateral nephrectomy within the first four days. Groups of control and PAN rats were killed at 21, 37, 52, 72 and 91 days. Renal sections were studied by immunofluorescence to quantitate interstitial macrophages, T lymphocytes and fibroblasts, and to characterize the deposition of the extracellular matrix (ECM) proteins (collagens I, III and IV, fibronectin and laminin) and the tissue inhibitor of the metalloproteinases (TIMP). Steady state concentrations of mRNA from the whole kidney for these ECM proteins, the metalloproteinases, TIMP, and transforming growth factor beta (TGF-β1) were quantitated by Northern blot analysis. Significant increases in the number of interstitial macrophages and T lymphocytes were found in the PAN rat groups compared to that in controls. All ECM proteins examined were quantitatively increased in the tubulointerstitium of PAN rats. The pattern of distribution of some ECM proteins was also modified in experimental animals. TIMP was increased in the interstitium of PAN rats; at later times, TIMP was most prominent in sclerotic regions of the glomeruli and in tubular protein droplets. Northern blot analysis revealed increased steady-state mRNA levels for components of each of the ECM proteins, no change for the metalloproteinases—stromelysin or collagenase—and a marked increase for TIMP and TGF-β1 in PAN animals. The results of this study suggest that the diffuse interstitial fibrosis found in chronic PAN nephrosis results from both increased production of ECM proteins and decreased matrix degradation.</description><subject>Albuminuria - etiology</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Chronic Disease</subject><subject>Creatinine - blood</subject><subject>Disease Models, Animal</subject><subject>Extracellular Matrix Proteins - genetics</subject><subject>Extracellular Matrix Proteins - metabolism</subject><subject>Female</subject><subject>Fibrosis</subject><subject>Gene Expression</subject><subject>Glycoproteins - genetics</subject><subject>Glycoproteins - metabolism</subject><subject>Interstitial nephritis</subject><subject>Macrophages - metabolism</subject><subject>Macrophages - pathology</subject><subject>Medical sciences</subject><subject>Metalloendopeptidases - antagonists & inhibitors</subject><subject>Metalloendopeptidases - genetics</subject><subject>Nephrology. Urinary tract diseases</subject><subject>Nephropathies. Renovascular diseases. Renal failure</subject><subject>Nephrosis - etiology</subject><subject>Nephrosis - metabolism</subject><subject>Nephrosis - pathology</subject><subject>Puromycin Aminonucleoside</subject><subject>Rats</subject><subject>Rats, Inbred Lew</subject><subject>Tissue Inhibitor of Metalloproteinases</subject><subject>Transforming Growth Factor beta - genetics</subject><issn>0085-2538</issn><issn>1523-1755</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1991</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNptkEFr3DAQRkVI2G7TnHou8aH0EryVLEuWjiW0TSCQFnIXsjzKTtcrbyQ70H8fbbxsLjkNw_f4ZniEfGZ0xShX3ze4YlqzFWf0hCyZqHjJGiFOyZJSJcpKcPWBfEzpH8275nRBFqyRFad8Sf7-seN6eIQACVMx-ALDCDGNOKLtC49tHPYBhsKt4xDQFbspYoDCbjEMYXI9ZKCDIsBu_cp-Imfe9gkuDvOcPPz6-XB9U97d_769_nFXulrJsQQvnXDK0kYJaLWUvlat0KxqaymZqLXtaqc891RKQVmtrAPt6s4LaIB1_Jx8m2t3cXiaII1mi8lB39sAw5RMUwklay0zeDWDLr-XInizi7i18b9h1Oz9mQ2avT-T_WX6y6F2arfQvbGzsJx_PeQ2Odv7aIPDdMQE1Vm_yNjljAU7ThGO-Qb3l-ZDYiYgO3pGiCY5hOCgwwhuNN2A7z74AmXelb8</recordid><startdate>19911201</startdate><enddate>19911201</enddate><creator>Jones, Colin L.</creator><creator>Buch, Shilpa</creator><creator>Post, Martin</creator><creator>McCulloch, Lori</creator><creator>Liu, Elaine</creator><creator>Eddy, Allison A.</creator><general>Elsevier Inc</general><general>Nature Publishing</general><scope>6I.</scope><scope>AAFTH</scope><scope>IQODW</scope><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>7X8</scope></search><sort><creationdate>19911201</creationdate><title>Pathogenesis of interstitial fibrosis in chronic purine aminonucleoside nephrosis</title><author>Jones, Colin L. ; Buch, Shilpa ; Post, Martin ; McCulloch, Lori ; Liu, Elaine ; Eddy, Allison A.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c486t-ef6c5c8a0785eb966f48b5912b4661549ad4c8f3f06650148ace9c4df5e7e1d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1991</creationdate><topic>Albuminuria - etiology</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Chronic Disease</topic><topic>Creatinine - blood</topic><topic>Disease Models, Animal</topic><topic>Extracellular Matrix Proteins - genetics</topic><topic>Extracellular Matrix Proteins - metabolism</topic><topic>Female</topic><topic>Fibrosis</topic><topic>Gene Expression</topic><topic>Glycoproteins - genetics</topic><topic>Glycoproteins - metabolism</topic><topic>Interstitial nephritis</topic><topic>Macrophages - metabolism</topic><topic>Macrophages - pathology</topic><topic>Medical sciences</topic><topic>Metalloendopeptidases - antagonists & inhibitors</topic><topic>Metalloendopeptidases - genetics</topic><topic>Nephrology. Urinary tract diseases</topic><topic>Nephropathies. Renovascular diseases. Renal failure</topic><topic>Nephrosis - etiology</topic><topic>Nephrosis - metabolism</topic><topic>Nephrosis - pathology</topic><topic>Puromycin Aminonucleoside</topic><topic>Rats</topic><topic>Rats, Inbred Lew</topic><topic>Tissue Inhibitor of Metalloproteinases</topic><topic>Transforming Growth Factor beta - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Jones, Colin L.</creatorcontrib><creatorcontrib>Buch, Shilpa</creatorcontrib><creatorcontrib>Post, Martin</creatorcontrib><creatorcontrib>McCulloch, Lori</creatorcontrib><creatorcontrib>Liu, Elaine</creatorcontrib><creatorcontrib>Eddy, Allison A.</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</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>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Kidney international</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Jones, Colin L.</au><au>Buch, Shilpa</au><au>Post, Martin</au><au>McCulloch, Lori</au><au>Liu, Elaine</au><au>Eddy, Allison A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Pathogenesis of interstitial fibrosis in chronic purine aminonucleoside nephrosis</atitle><jtitle>Kidney international</jtitle><addtitle>Kidney Int</addtitle><date>1991-12-01</date><risdate>1991</risdate><volume>40</volume><issue>6</issue><spage>1020</spage><epage>1031</epage><pages>1020-1031</pages><issn>0085-2538</issn><eissn>1523-1755</eissn><coden>KDYIA5</coden><abstract>Pathogenesis of interstitial fibrosis in chronic purine aminonucleoside nephrosis. A cellular and molecular approach was used to gain new insight into the pathogenesis of interstitial fibrosis in chronic purine aminonucleoside nephrosis (PAN) nephrosis. Thirty experimental rats (PAN rats) were given 15 mg/100 g body wt of i.p. PAN at time 0, followed by 4.3 mg/100 g body wt i.p. on days 20, 27 and 34; 25 control rats received i.p. saline at the same time intervals. All rats had a right unilateral nephrectomy within the first four days. Groups of control and PAN rats were killed at 21, 37, 52, 72 and 91 days. Renal sections were studied by immunofluorescence to quantitate interstitial macrophages, T lymphocytes and fibroblasts, and to characterize the deposition of the extracellular matrix (ECM) proteins (collagens I, III and IV, fibronectin and laminin) and the tissue inhibitor of the metalloproteinases (TIMP). Steady state concentrations of mRNA from the whole kidney for these ECM proteins, the metalloproteinases, TIMP, and transforming growth factor beta (TGF-β1) were quantitated by Northern blot analysis. Significant increases in the number of interstitial macrophages and T lymphocytes were found in the PAN rat groups compared to that in controls. All ECM proteins examined were quantitatively increased in the tubulointerstitium of PAN rats. The pattern of distribution of some ECM proteins was also modified in experimental animals. TIMP was increased in the interstitium of PAN rats; at later times, TIMP was most prominent in sclerotic regions of the glomeruli and in tubular protein droplets. Northern blot analysis revealed increased steady-state mRNA levels for components of each of the ECM proteins, no change for the metalloproteinases—stromelysin or collagenase—and a marked increase for TIMP and TGF-β1 in PAN animals. The results of this study suggest that the diffuse interstitial fibrosis found in chronic PAN nephrosis results from both increased production of ECM proteins and decreased matrix degradation.</abstract><cop>New York, NY</cop><pub>Elsevier Inc</pub><pmid>1762303</pmid><doi>10.1038/ki.1991.310</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Albuminuria - etiology Animals Biological and medical sciences Chronic Disease Creatinine - blood Disease Models, Animal Extracellular Matrix Proteins - genetics Extracellular Matrix Proteins - metabolism Female Fibrosis Gene Expression Glycoproteins - genetics Glycoproteins - metabolism Interstitial nephritis Macrophages - metabolism Macrophages - pathology Medical sciences Metalloendopeptidases - antagonists & inhibitors Metalloendopeptidases - genetics Nephrology. Urinary tract diseases Nephropathies. Renovascular diseases. Renal failure Nephrosis - etiology Nephrosis - metabolism Nephrosis - pathology Puromycin Aminonucleoside Rats Rats, Inbred Lew Tissue Inhibitor of Metalloproteinases Transforming Growth Factor beta - genetics |
title | Pathogenesis of interstitial fibrosis in chronic purine aminonucleoside nephrosis |
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