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Adiponectin Protects Mouse Podocytes from Acid Ceramidase Inhibition‐Induced Injury
Author(s) -
Koka Saisudha,
Xia Min,
Conley Sabena M,
Gehr Todd W,
Li Ningjun,
Li PinLan,
Boini Krishna M
Publication year - 2016
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/fasebj.30.1_supplement.739.16
Subject(s) - podocyte , podocin , adiponectin , endocrinology , medicine , chemistry , microbiology and biotechnology , biology , kidney , insulin resistance , insulin , proteinuria
Our recent studies have demonstrated that acid ceramidase (AC) contributes to the regulation of podocyte function and that the defect of AC gene expression triggers podocyte injury ultimately resulting in obesity‐associated end‐stage renal disease. However, it remains unknown how the inhibition of AC leads to podocyte dysfunction and injury. The current study addressed whether adipokine, adiponectin antagonizes AC inhibition‐induced damage in cultured mouse podocytes. Western blot analysis showed that adiponectin treatment dose dependently increased the acid ceramidase expression in podocytes. Confocal and RT‐PCR analyses showed that AC inhibitor, D‐NMAPPD decreased the podocin expression compared to control cells. However, prior treatment with adiponectin attenuated the D‐NMAPPD‐induced podocin decrease. Furthermore, adiponectin treatment was found to preserve podocyte morphology by maintaining the distinct arrangement of F‐actin fibers normally lost in response to D‐NMAPPD. It also prevented podocyte dysfunction by restoring D‐NMAPD‐induced suppression of VEGF production and secretion. By electromagnetic spin resonance, AC inhibitor was shown to increase superoxide production 1.8 folds compared to control podocytes, which was inhibited by adiponectin. Functionally, AC inhibitor, D‐NMAPPD treatment significantly increased the cell permeability in podocytes compared to control cells (Control: 1 ± 0.1 vs. D‐NMAPPD: 1.6 ± 0.1), and adiponectin attenuated the D‐NMAPPD‐induced increases in cell permeability. In conclusion, our observations suggest that adiponectin may exert an antagonistic action on acid ceramidase inhibition‐induced podocyte dysfunction and injury. Support or Funding Information Supported by NIH grants DK104031 and DK54927.