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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Veröffentlicht in:The FASEB journal 2003-04, Vol.17 (6), p.682-684
Hauptverfasser: Bek, Martin J., Wahle, Stephanie, Müller, Barbara, Benzing, Thomas, Huber, Tobias B., Kretzler, Matthias, Cohen, Clemen, Busse‐Grawitz, Andrea, Pavenstädt, Hermann
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container_end_page 684
container_issue 6
container_start_page 682
container_title The FASEB journal
container_volume 17
creator Bek, Martin J.
Wahle, Stephanie
Müller, Barbara
Benzing, Thomas
Huber, Tobias B.
Kretzler, Matthias
Cohen, Clemen
Busse‐Grawitz, Andrea
Pavenstädt, Hermann
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.
doi_str_mv 10.1096/fj.02-0250fje
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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. 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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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source MEDLINE; Wiley Journals; Alma/SFX Local Collection
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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