Stra13, a prostaglandin E2-induced gene, regulates the cellular redox state of podocytes.
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.
Bek
Martin J
MJ
Department of Medicine, Division of Nephrology, Freiburg University Hospital, Freiburg, Germany.
Wahle
Stephanie
S
Müller
Barbara
B
Benzing
Thomas
T
Huber
Tobias B
TB
Kretzler
Matthias
M
Cohen
Clemen
C
Busse-Grawitz
Andrea
A
Pavenstädt
Hermann
H
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D015153:Blotting, Western; D005576:Colforsin / Q000494:pharmacology; D016373:DNA, Antisense / Q000235:genetics / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics / Q000378:metabolism; D051547:Heme Oxygenase-1; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D007678:Kidney Glomerulus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008565:Membrane Proteins; D051379:Mice; D019255:NADPH Oxidases / Q000378:metabolism; D010084:Oxidation-Reduction; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000494:pharmacology; D014212:Tretinoin / Q000494:pharmacology
D051792:Basic Helix-Loop-Helix Proteins; D005576:Colforsin; D016373:DNA, Antisense; D015232:Dinoprostone; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; D018398:Homeodomain Proteins; D008565:Membrane Proteins; D019255:NADPH Oxidases; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D014212:Tretinoin; C491539:Bhlhe40 protein, mouse; C496542:Hmox1 protein, mouse