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Article

Pigment epithelium‑derived factor protects human glomerular mesangial cells from diabetes via NOXO1‑iNOS suppression

  • Authors:
    • Ling Gao
    • Yingjie Hu
    • Jing Li
  • View Affiliations / Copyright

    Affiliations: Department of Endocrinology, Renmin Hospital of Wuhan University, Wuhan 430060, P.R. China
  • Pages: 7855-7863
    |
    Published online on: September 20, 2017
       https://doi.org/10.3892/mmr.2017.7563
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Abstract

The authors previously reported that pigment epithelium‑derived factor (PEDF) protects the diabetic kidney from fibrosis via its anti‑oxidative effects. However, the underlying molecular mechanism has never been revealed. The present study aimed to investigate how PEDF protects mesangial cells from diabetes induced damage. Human mesangial cells were exposed to a diabetic environment [30 mmol/l glucose and 200 mg advanced glycation end products (AGEs)] in the absence or presence of PEDF (200 mg/l). The superoxide and peroxynitrite productions were measured by fluorescent assay. The nicotinamide adenine dinucleotide phosphate (NAPDH) oxidases (NOXs; isoforms NOX1, NOX2, and NOX4), NADPH oxidase organizer 1 (NOXO1), DHFR, endothelial nitric oxide synthase (iNOS) and phospho‑p38MAPK (p‑p38) protein levels were also examined to explore the possible mechanism of the PEDF anti‑oxidative properties. The fibrogenesis of mesangial cells in diabetes was associated with increased superoxide generation and peroxynitrite production via iNOS induction and uncoupling. However, elevated transforming growth factor‑β level, reactive oxygen species (ROS) overproduction, iNOS induction and uncoupling were all reversed by NOXO1 suppression following PEDF treatment or NOXO1 silencing. Furthermore, the p38MAPK inhibition only attenuated the ROS/peroxynitrite production partially via abolishment of iNOS induction, however had no effect on iNOS uncoupling and its regulating enzyme: DHFR suppression. PEDF prevented oxidative stress and protected mesangial cells from fibrogenesis in a diabetic environment via dual effects mediated by NOXO1 inhibitory prevention of iNOS induction through p38MAPK inactivation and effects on iNOS coupling through DHFR restoration.
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Copy and paste a formatted citation
Spandidos Publications style
Gao L, Hu Y and Li J: Pigment epithelium‑derived factor protects human glomerular mesangial cells from diabetes via NOXO1‑iNOS suppression. Mol Med Rep 16: 7855-7863, 2017.
APA
Gao, L., Hu, Y., & Li, J. (2017). Pigment epithelium‑derived factor protects human glomerular mesangial cells from diabetes via NOXO1‑iNOS suppression. Molecular Medicine Reports, 16, 7855-7863. https://doi.org/10.3892/mmr.2017.7563
MLA
Gao, L., Hu, Y., Li, J."Pigment epithelium‑derived factor protects human glomerular mesangial cells from diabetes via NOXO1‑iNOS suppression". Molecular Medicine Reports 16.5 (2017): 7855-7863.
Chicago
Gao, L., Hu, Y., Li, J."Pigment epithelium‑derived factor protects human glomerular mesangial cells from diabetes via NOXO1‑iNOS suppression". Molecular Medicine Reports 16, no. 5 (2017): 7855-7863. https://doi.org/10.3892/mmr.2017.7563
Copy and paste a formatted citation
x
Spandidos Publications style
Gao L, Hu Y and Li J: Pigment epithelium‑derived factor protects human glomerular mesangial cells from diabetes via NOXO1‑iNOS suppression. Mol Med Rep 16: 7855-7863, 2017.
APA
Gao, L., Hu, Y., & Li, J. (2017). Pigment epithelium‑derived factor protects human glomerular mesangial cells from diabetes via NOXO1‑iNOS suppression. Molecular Medicine Reports, 16, 7855-7863. https://doi.org/10.3892/mmr.2017.7563
MLA
Gao, L., Hu, Y., Li, J."Pigment epithelium‑derived factor protects human glomerular mesangial cells from diabetes via NOXO1‑iNOS suppression". Molecular Medicine Reports 16.5 (2017): 7855-7863.
Chicago
Gao, L., Hu, Y., Li, J."Pigment epithelium‑derived factor protects human glomerular mesangial cells from diabetes via NOXO1‑iNOS suppression". Molecular Medicine Reports 16, no. 5 (2017): 7855-7863. https://doi.org/10.3892/mmr.2017.7563
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