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F. Drago, C. Bucolo, M. L. Amadio, G. Scapagnini, G. Lupo, S. Govoni, A. Pascale; PKCbetaII/HuR/VEGF: a New Molecular Cascade in Retinal Pericytes for the Regulation of VEGF Gene Expression. Invest. Ophthalmol. Vis. Sci. 2008;49(13):5365.
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VEGF-induced new vessels formation is a key event in diabetic retinopathy, a severe progressive multistage pathology. Literature data indicate that Protein Kinase C (PKC) is involved in the control of VEGF expression, but no data are so far available on the molecular pathway underlying this process. We investigated whether PKCβII could control VEGF expression at posttranslational level via the mRNA stabilizing human embryonic lethal abnormal vision (ELAV)-like protein, HuR.
Retinal bovine pericytes were exposed to phorbol esters to activate PKC. The direct interaction/activation of PKCβII with HuR was examined by western blotting, immunoprecipitation and immunocytochemistry. The binding of HuR to VEGF was assessed in ribonucleoproteic complexes by immunoprecipitation coupled with real-time PCR. VEGF was immunoprecipitated from the medium.
The data show that PKCβII activation is responsible, through the RNA-binding protein HuR, of the increase of VEGF protein content and its release in the medium. The specificity of the PKCβII involvement was confirmed using a selective inhibitor. Following acute high-glucose insult this pathway seemed still functioning, suggesting that a brief pick of glucose does not compromise this molecular cascade in pericytes.
We suggest the existence of a new molecular cascade, operating in retinal bovine pericytes and involving PKCβII, HuR, and VEGF. A better understanding on this new pathway could open novel opportunities for the development of innovative pharmacological therapies useful in pathologies where VEGF plays a key role such as in diabetic retinopathy.
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