The importance of cellular VEGF bioactivity in the development of glomerular disease.

The bioactivity of glomerular VEGF (or activity of available VEGF) is critical to the physiological maintenance of the glomerular filtration barrier. Disturbances in glomerular VEGF expression have been linked to numerous glomerulopathies, highlighting its importance in disease progression within the kidney. However, the changes in expression are not consistent between conditions; enhanced expression sometimes appears to have a renoprotective effect, yet at other times it appears destructive. Also, the level of expression can change with the progression of disease. This review focuses on how other cellular factors, such as TGF-beta and nitric oxide, work in concert to affect the bioactivity, which is not necessarily the same as the expression of VEGF, in different glomerulopathies and attempts to explain some of the paradoxes between glomerulopathies. In conclusion, the bioactivity of glomerular VEGF is regulated by many factors that are themselves moderated by changes in the local glomerular environment, such as mechanical strain and hyperglycaemia. Thus, to understand VEGF signalling in glomerular disease progression, we must examine it in the context of other appropriate cellular factors.