Stra13, a prostaglandin E2‐induced gene, regulates the cellular redox state of podocytes
ABSTRACT Podocyte injury is a central mechanism in the pathogenesis of proteinuria. Prostaglandin E2 (PGE2) has been suggested to protect podocytes from cellular injury. Here we investigated whether PGE2‐induced gene expression accounts for the protective role of PGE2 in podocytes. Using a suppressi...
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description | ABSTRACT
Podocyte injury is a central mechanism in the pathogenesis of proteinuria. Prostaglandin E2 (PGE2) has been suggested to protect podocytes from cellular injury. Here we investigated whether PGE2‐induced gene expression accounts for the protective role of PGE2 in podocytes. Using a suppressive‐subtractive hybridization method, we isolated a differentially expressed clone that was identified as Stra13, a recently described retinoic acid‐inducible gene. PGE2, forskolin, and retinoic acid induced a time‐dependent up‐regulation of Stra13 mRNA and protein expression in podocytes. To test the function of Stra13 in podocytes, Stra13 was overexpressed by using retroviral gene transfer. Compared with control cells, cells overexpressing Stra13 showed markedly reduced NADPH‐dependent superoxid anion generation. Furthermore, expression of heme oxygenase 1 (HO‐1) was increased in podocytes overexpressing Stra13. HO‐1 plays an important protective role in the defense against reactive oxygen species (ROS). After stimulation with exogenous ROS, Stra13‐overexpressing podocytes were more resistant to oxidative stress than were control cells. Our data indicate that Stra13 may play an important protective role against oxidative stress in podocytes. ROS are involved in the pathogenesis of glomerular inflammation in several forms of glomerulonephritis. Therefore, knowledge about protective mechanisms may provide insight into new therapeutic strategies for glomerulopathies. |
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Podocyte injury is a central mechanism in the pathogenesis of proteinuria. Prostaglandin E2 (PGE2) has been suggested to protect podocytes from cellular injury. Here we investigated whether PGE2‐induced gene expression accounts for the protective role of PGE2 in podocytes. Using a suppressive‐subtractive hybridization method, we isolated a differentially expressed clone that was identified as Stra13, a recently described retinoic acid‐inducible gene. PGE2, forskolin, and retinoic acid induced a time‐dependent up‐regulation of Stra13 mRNA and protein expression in podocytes. To test the function of Stra13 in podocytes, Stra13 was overexpressed by using retroviral gene transfer. Compared with control cells, cells overexpressing Stra13 showed markedly reduced NADPH‐dependent superoxid anion generation. Furthermore, expression of heme oxygenase 1 (HO‐1) was increased in podocytes overexpressing Stra13. HO‐1 plays an important protective role in the defense against reactive oxygen species (ROS). After stimulation with exogenous ROS, Stra13‐overexpressing podocytes were more resistant to oxidative stress than were control cells. Our data indicate that Stra13 may play an important protective role against oxidative stress in podocytes. ROS are involved in the pathogenesis of glomerular inflammation in several forms of glomerulonephritis. Therefore, knowledge about protective mechanisms may provide insight into new therapeutic strategies for glomerulopathies.</description><identifier>ISSN: 0892-6638</identifier><identifier>EISSN: 1530-6860</identifier><identifier>DOI: 10.1096/fj.02-0250fje</identifier><identifier>PMID: 12594185</identifier><language>eng</language><publisher>United States: Federation of American Societies for Experimental Biology</publisher><subject>Animals ; Basic Helix-Loop-Helix Transcription Factors ; Blotting, Western ; Colforsin - pharmacology ; cytoprotection ; Dinoprostone - pharmacology ; DNA, Antisense - genetics ; DNA, Antisense - pharmacology ; Gene Expression Regulation - drug effects ; Heme Oxygenase (Decyclizing) - genetics ; Heme Oxygenase (Decyclizing) - metabolism ; Heme Oxygenase-1 ; Homeodomain Proteins - genetics ; Homeodomain Proteins - metabolism ; Kidney Glomerulus - cytology ; Kidney Glomerulus - drug effects ; Kidney Glomerulus - metabolism ; Membrane Proteins ; Mice ; NADPH Oxidases - metabolism ; Oxidation-Reduction ; oxidative stress ; Reactive Oxygen Species - pharmacology ; retinoic acid ; RNA, Messenger - drug effects ; RNA, Messenger - genetics ; RNA, Messenger - metabolism ; Tretinoin - pharmacology</subject><ispartof>The FASEB journal, 2003-04, Vol.17 (6), p.682-684</ispartof><rights>FASEB</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1096%2Ffj.02-0250fje$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1096%2Ffj.02-0250fje$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12594185$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Bek, Martin J.</creatorcontrib><creatorcontrib>Wahle, Stephanie</creatorcontrib><creatorcontrib>Müller, Barbara</creatorcontrib><creatorcontrib>Benzing, Thomas</creatorcontrib><creatorcontrib>Huber, Tobias B.</creatorcontrib><creatorcontrib>Kretzler, Matthias</creatorcontrib><creatorcontrib>Cohen, Clemen</creatorcontrib><creatorcontrib>Busse‐Grawitz, Andrea</creatorcontrib><creatorcontrib>Pavenstädt, Hermann</creatorcontrib><title>Stra13, a prostaglandin E2‐induced gene, regulates the cellular redox state of podocytes</title><title>The FASEB journal</title><addtitle>FASEB J</addtitle><description>ABSTRACT
Podocyte injury is a central mechanism in the pathogenesis of proteinuria. Prostaglandin E2 (PGE2) has been suggested to protect podocytes from cellular injury. Here we investigated whether PGE2‐induced gene expression accounts for the protective role of PGE2 in podocytes. Using a suppressive‐subtractive hybridization method, we isolated a differentially expressed clone that was identified as Stra13, a recently described retinoic acid‐inducible gene. PGE2, forskolin, and retinoic acid induced a time‐dependent up‐regulation of Stra13 mRNA and protein expression in podocytes. To test the function of Stra13 in podocytes, Stra13 was overexpressed by using retroviral gene transfer. Compared with control cells, cells overexpressing Stra13 showed markedly reduced NADPH‐dependent superoxid anion generation. Furthermore, expression of heme oxygenase 1 (HO‐1) was increased in podocytes overexpressing Stra13. HO‐1 plays an important protective role in the defense against reactive oxygen species (ROS). After stimulation with exogenous ROS, Stra13‐overexpressing podocytes were more resistant to oxidative stress than were control cells. Our data indicate that Stra13 may play an important protective role against oxidative stress in podocytes. ROS are involved in the pathogenesis of glomerular inflammation in several forms of glomerulonephritis. Therefore, knowledge about protective mechanisms may provide insight into new therapeutic strategies for glomerulopathies.</description><subject>Animals</subject><subject>Basic Helix-Loop-Helix Transcription Factors</subject><subject>Blotting, Western</subject><subject>Colforsin - pharmacology</subject><subject>cytoprotection</subject><subject>Dinoprostone - pharmacology</subject><subject>DNA, Antisense - genetics</subject><subject>DNA, Antisense - pharmacology</subject><subject>Gene Expression Regulation - drug effects</subject><subject>Heme Oxygenase (Decyclizing) - genetics</subject><subject>Heme Oxygenase (Decyclizing) - metabolism</subject><subject>Heme Oxygenase-1</subject><subject>Homeodomain Proteins - genetics</subject><subject>Homeodomain Proteins - metabolism</subject><subject>Kidney Glomerulus - cytology</subject><subject>Kidney Glomerulus - drug effects</subject><subject>Kidney Glomerulus - metabolism</subject><subject>Membrane Proteins</subject><subject>Mice</subject><subject>NADPH Oxidases - metabolism</subject><subject>Oxidation-Reduction</subject><subject>oxidative stress</subject><subject>Reactive Oxygen Species - pharmacology</subject><subject>retinoic acid</subject><subject>RNA, Messenger - drug effects</subject><subject>RNA, Messenger - genetics</subject><subject>RNA, Messenger - metabolism</subject><subject>Tretinoin - pharmacology</subject><issn>0892-6638</issn><issn>1530-6860</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkL9OwzAQxi0EoqUwsiJPTE0524kbs0GVAlUlhsLCYjnxuaRKk5I_gm48As_Ik-CKIqbTd_e7030fIecMRgyUvHKrEfAAeARuhQekzyIBgYwlHJI-xIoHUoq4R06aZgUADJg8Jj3GIxWyOOqTl0VbGyaG1NBNXTWtWRamtHlJE_79-ZWXtsvQ0iWWOKQ1LrvCtNjQ9hVphkXhZe3btvqgfrVFWjm6qWyVbT11So6cKRo829cBeZ4mT5P7YP549zC5mQcbNhZJwEIT2iiKY56FPLXjkEMsuUHumIpixzNrME19zWQqXWq5ApFZp0JpFFrlxIBc_t71Bt46bFq9zpvdd6bEqmv0WDDvVSgPXuzBLl2j1Zs6X5t6q__S8MD1L_CeF7j9n4PeRa3dSgPX-6j1dHHLpzPgOz2dJeIH7l109g</recordid><startdate>200304</startdate><enddate>200304</enddate><creator>Bek, Martin J.</creator><creator>Wahle, Stephanie</creator><creator>Müller, Barbara</creator><creator>Benzing, Thomas</creator><creator>Huber, Tobias B.</creator><creator>Kretzler, Matthias</creator><creator>Cohen, Clemen</creator><creator>Busse‐Grawitz, Andrea</creator><creator>Pavenstädt, Hermann</creator><general>Federation of American Societies for Experimental Biology</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope></search><sort><creationdate>200304</creationdate><title>Stra13, a prostaglandin E2‐induced gene, regulates the cellular redox state of podocytes</title><author>Bek, Martin J. ; Wahle, Stephanie ; Müller, Barbara ; Benzing, Thomas ; Huber, Tobias B. ; Kretzler, Matthias ; Cohen, Clemen ; Busse‐Grawitz, Andrea ; Pavenstädt, Hermann</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p173E-14a4d55882c42bd7420862ae2f1958f2cdaebbf2cc6b6fbd2903cdf946a9ed9f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Animals</topic><topic>Basic Helix-Loop-Helix Transcription Factors</topic><topic>Blotting, Western</topic><topic>Colforsin - pharmacology</topic><topic>cytoprotection</topic><topic>Dinoprostone - pharmacology</topic><topic>DNA, Antisense - genetics</topic><topic>DNA, Antisense - pharmacology</topic><topic>Gene Expression Regulation - drug effects</topic><topic>Heme Oxygenase (Decyclizing) - genetics</topic><topic>Heme Oxygenase (Decyclizing) - metabolism</topic><topic>Heme Oxygenase-1</topic><topic>Homeodomain Proteins - genetics</topic><topic>Homeodomain Proteins - metabolism</topic><topic>Kidney Glomerulus - cytology</topic><topic>Kidney Glomerulus - drug effects</topic><topic>Kidney Glomerulus - metabolism</topic><topic>Membrane Proteins</topic><topic>Mice</topic><topic>NADPH Oxidases - metabolism</topic><topic>Oxidation-Reduction</topic><topic>oxidative stress</topic><topic>Reactive Oxygen Species - pharmacology</topic><topic>retinoic acid</topic><topic>RNA, Messenger - drug effects</topic><topic>RNA, Messenger - genetics</topic><topic>RNA, Messenger - metabolism</topic><topic>Tretinoin - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Bek, Martin J.</creatorcontrib><creatorcontrib>Wahle, Stephanie</creatorcontrib><creatorcontrib>Müller, Barbara</creatorcontrib><creatorcontrib>Benzing, Thomas</creatorcontrib><creatorcontrib>Huber, Tobias B.</creatorcontrib><creatorcontrib>Kretzler, Matthias</creatorcontrib><creatorcontrib>Cohen, Clemen</creatorcontrib><creatorcontrib>Busse‐Grawitz, Andrea</creatorcontrib><creatorcontrib>Pavenstädt, Hermann</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><jtitle>The FASEB journal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bek, Martin J.</au><au>Wahle, Stephanie</au><au>Müller, Barbara</au><au>Benzing, Thomas</au><au>Huber, Tobias B.</au><au>Kretzler, Matthias</au><au>Cohen, Clemen</au><au>Busse‐Grawitz, Andrea</au><au>Pavenstädt, Hermann</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Stra13, a prostaglandin E2‐induced gene, regulates the cellular redox state of podocytes</atitle><jtitle>The FASEB journal</jtitle><addtitle>FASEB J</addtitle><date>2003-04</date><risdate>2003</risdate><volume>17</volume><issue>6</issue><spage>682</spage><epage>684</epage><pages>682-684</pages><issn>0892-6638</issn><eissn>1530-6860</eissn><abstract>ABSTRACT
Podocyte injury is a central mechanism in the pathogenesis of proteinuria. Prostaglandin E2 (PGE2) has been suggested to protect podocytes from cellular injury. Here we investigated whether PGE2‐induced gene expression accounts for the protective role of PGE2 in podocytes. Using a suppressive‐subtractive hybridization method, we isolated a differentially expressed clone that was identified as Stra13, a recently described retinoic acid‐inducible gene. PGE2, forskolin, and retinoic acid induced a time‐dependent up‐regulation of Stra13 mRNA and protein expression in podocytes. To test the function of Stra13 in podocytes, Stra13 was overexpressed by using retroviral gene transfer. Compared with control cells, cells overexpressing Stra13 showed markedly reduced NADPH‐dependent superoxid anion generation. Furthermore, expression of heme oxygenase 1 (HO‐1) was increased in podocytes overexpressing Stra13. HO‐1 plays an important protective role in the defense against reactive oxygen species (ROS). After stimulation with exogenous ROS, Stra13‐overexpressing podocytes were more resistant to oxidative stress than were control cells. Our data indicate that Stra13 may play an important protective role against oxidative stress in podocytes. ROS are involved in the pathogenesis of glomerular inflammation in several forms of glomerulonephritis. Therefore, knowledge about protective mechanisms may provide insight into new therapeutic strategies for glomerulopathies.</abstract><cop>United States</cop><pub>Federation of American Societies for Experimental Biology</pub><pmid>12594185</pmid><doi>10.1096/fj.02-0250fje</doi><tpages>25</tpages></addata></record> |
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subjects | Animals Basic Helix-Loop-Helix Transcription Factors Blotting, Western Colforsin - pharmacology cytoprotection Dinoprostone - pharmacology DNA, Antisense - genetics DNA, Antisense - pharmacology Gene Expression Regulation - drug effects Heme Oxygenase (Decyclizing) - genetics Heme Oxygenase (Decyclizing) - metabolism Heme Oxygenase-1 Homeodomain Proteins - genetics Homeodomain Proteins - metabolism Kidney Glomerulus - cytology Kidney Glomerulus - drug effects Kidney Glomerulus - metabolism Membrane Proteins Mice NADPH Oxidases - metabolism Oxidation-Reduction oxidative stress Reactive Oxygen Species - pharmacology retinoic acid RNA, Messenger - drug effects RNA, Messenger - genetics RNA, Messenger - metabolism Tretinoin - pharmacology |
title | Stra13, a prostaglandin E2‐induced gene, regulates the cellular redox state of podocytes |
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