Stra13, a prostaglandin E2-induced gene, regulates the cellular redox state of podocytes
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Stra13, a prostaglandin E2-induced gene, regulates the cellular redox state of podocytes. / Bek, Martin J; Wahle, Stephanie; Müller, Barbara; Benzing, Thomas; Huber, Tobias B; Kretzler, Matthias; Cohen, Clemen; Busse-Grawitz, Andrea; Pavenstädt, Hermann.
in: FASEB J, Jahrgang 17, Nr. 6, 04.2003, S. 682-4.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - Stra13, a prostaglandin E2-induced gene, regulates the cellular redox state of podocytes
AU - Bek, Martin J
AU - Wahle, Stephanie
AU - Müller, Barbara
AU - Benzing, Thomas
AU - Huber, Tobias B
AU - Kretzler, Matthias
AU - Cohen, Clemen
AU - Busse-Grawitz, Andrea
AU - Pavenstädt, Hermann
PY - 2003/4
Y1 - 2003/4
N2 - 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.
AB - 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.
KW - Animals
KW - Basic Helix-Loop-Helix Transcription Factors
KW - Blotting, Western
KW - Colforsin
KW - DNA, Antisense
KW - Dinoprostone
KW - Gene Expression Regulation
KW - Heme Oxygenase (Decyclizing)
KW - Heme Oxygenase-1
KW - Homeodomain Proteins
KW - Kidney Glomerulus
KW - Membrane Proteins
KW - Mice
KW - NADPH Oxidase
KW - Oxidation-Reduction
KW - RNA, Messenger
KW - Reactive Oxygen Species
KW - Tretinoin
KW - Journal Article
U2 - 10.1096/fj.02-0250fje
DO - 10.1096/fj.02-0250fje
M3 - SCORING: Journal article
C2 - 12594185
VL - 17
SP - 682
EP - 684
JO - FASEB J
JF - FASEB J
SN - 0892-6638
IS - 6
ER -