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Stra13, a prostaglandin E 2 ‐induced gene, regulates the cellular redox state of podocytes
Author(s) -
Bek Martin J.,
Wahle Stephanie,
Müller Barbara,
Benzing Thomas,
Huber Tobias B.,
Kretzler Matthias,
Cohen Clemen,
BusseGrawitz Andrea,
Pavenstädt Hermann
Publication year - 2003
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.02-0250fje
Subject(s) - oxidative stress , bradykinin , podocyte , angiotensin ii , heme oxygenase , endocrinology , biology , medicine , microbiology and biotechnology , receptor , heme , kidney , biochemistry , proteinuria , enzyme
ABSTRACT Podocyte injury is a central mechanism in the pathogenesis of proteinuria. Prostaglandin E 2 (PGE 2 ) has been suggested to protect podocytes from cellular injury. Here we investigated whether PGE 2 ‐induced gene expression accounts for the protective role of PGE 2 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. PGE 2 , 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.