Abstract
Pigment epithelium-derived factor (PEDF) is a potent angiogenic inhibitor. Previous studies have shown that decreased ocular levels of PEDF are associated with diabetic retinopathy. However, the implication of PEDF expression in diabetic nephropathy has not been revealed. In the present study, we demonstrated for the first time that the expression of PEDF was decreased at both the mRNA and protein levels in the kidney of diabetic rats, whereas transforming growth factor-beta (TGF-beta) and fibronectin levels were increased in the same diabetic kidneys. As shown by immunohistochemistry, the decrease of PEDF expression occurs primarily in the glomeruli. In vitro studies showed that high concentrations of glucose significantly decreased PEDF secretion in primary human glomerular mesangial cells (HMCs), suggesting that hyperglycemia is a direct cause of the PEDF decrease in the kidney. Toward the function of PEDF, we showed that PEDF blocked the high-glucose-induced overexpression of TGF-beta, a major pathogenic factor in diabetic nephropathy, and fibronectin in primary HMCs, suggesting that PEDF may function as an endogenous inhibitor of TGF-beta expression and fibronectin production in glomeruli. Therefore, decreased expression of PEDF in diabetic kidneys may contribute to extracellular matrix overproduction and the development of diabetic nephropathy.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
