Antioxidants ameliorate the expression of vascular endothelial growth factor mediated by protein kinase C in diabetic podocytes

Eun Young Lee, Choon Hee Chung, Jung Hyun Kim, Hea Jung Joung, Sae Yong Hong

Research output: Contribution to journalArticlepeer-review

33 Citations (Scopus)

Abstract

Background: The increased production of reactive oxygen species (ROS) may be involved in the onset or development of diabetic vascular complications. The release of ROS from podocytes plays a role in the pathogenesis of glomerular damage in various experimental glomerular diseases. Although it is assumed that the podocyte injury also plays an important role in diabetic nephropathy, the mechanism is still unknown. Methods: Using a differentiated mouse podocyte cell line, we investigat ed: (1) whether a high level of ambient glucose increases the level of ROS, (2) whether the protein kinase C (PKC) pathway is involved in a high-glucose-induced generation of ROS and vascular endothelial growth factor (VEGF) and (3) whether antioxidants ameliorate PKC-mediated VEGF expression in diabetic milieu. Results: Intracellular ROS generation was significantly higher in high glucose than in control conditions in cultured podocytes. High ambient glucose also increased VEGF mRNA and protein expression. The high-glucose-induced increases in ROS and VEGF mRNA and protein by podocytes were effectively inhibited by pretreatment with various antioxidants and were completely restored by PKC inhibition. The results show that cultured mouse podocytes produce ROS in response to high glucose, and that PKC is involved in high-glucose-induced ROS and VEGF production by podocyte. Conclusion: Increased ROS in podocytes may play a role in the pathogenesis of podocyte injury in diabetic nephropathy.

Original languageEnglish
Pages (from-to)1496-1503
Number of pages8
JournalNephrology Dialysis Transplantation
Volume21
Issue number6
DOIs
Publication statusPublished - 2006 Jun

Bibliographical note

Funding Information:
Acknowledgements. This work was supported by grant no. R05-2002-000-00024-0 from the Basic Research Program of the Korea Science and Engineering Foundation. The authors are grateful to Dr Peter Mundel (Albert Einstein College of Medicine) for providing the conditionally immortalized mouse podocyte cell line. The authors also thank Zee Won Lee of the Korea Basic Science Institute (Daejeon, Korea) for technical assistance.

All Science Journal Classification (ASJC) codes

  • Nephrology
  • Transplantation

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