We have located links that may give you full text access.
Pigment epithelium‑derived factor protects human glomerular mesangial cells from diabetes via NOXO1‑iNOS suppression.
Molecular Medicine Reports 2017 November
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.
Full text links
Related Resources
Trending Papers
Challenges in Septic Shock: From New Hemodynamics to Blood Purification Therapies.Journal of Personalized Medicine 2024 Februrary 4
Molecular Targets of Novel Therapeutics for Diabetic Kidney Disease: A New Era of Nephroprotection.International Journal of Molecular Sciences 2024 April 4
The 'Ten Commandments' for the 2023 European Society of Cardiology guidelines for the management of endocarditis.European Heart Journal 2024 April 18
A Guide to the Use of Vasopressors and Inotropes for Patients in Shock.Journal of Intensive Care Medicine 2024 April 14
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app
All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.
By using this service, you agree to our terms of use and privacy policy.
Your Privacy Choices
You can now claim free CME credits for this literature searchClaim now
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app