PKCbetaII/HuR/VEGF: A new molecular cascade in retinal pericytes for the regulation of VEGF gene expression

Pharmacological Research : the Official Journal of the Italian Pharmacological Society
Marialaura AmadioAlessia Pascale

Abstract

Vascular endothelial growth factor (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, so far, no data are available on the molecular pathway underlying this process. Within this context, we suggest the existence of a new molecular cascade, operating in retinal bovine pericytes and involving PKCbetaII, the mRNA-stabilizing protein HuR, and VEGF. In particular we show that PKCbetaII activation is responsible, through the RNA-binding protein HuR, for the increase of VEGF protein content and its release in the medium. The specificity of the PKCbetaII involvement is confirmed by experiments performed with the LY379196 compound, a selective PKCbetaII inhibitor. Following acute high-glucose insult this pathway seems still functioning, suggesting that a brief exposure to glucose does not compromise this molecular cascade in pericytes. 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.

References

Aug 13, 1993·Cell·A B Sachs
Oct 1, 1996·The International Journal of Biochemistry & Cell Biology·R HovlandI F Pryme
Apr 16, 1998·The Journal of Biological Chemistry·N S LevyA P Levy
Apr 16, 1998·Diabetes Care·L P AielloR Klein
Jan 6, 1999·Proceedings of the National Academy of Sciences of the United States of America·J D Keene
Sep 10, 1999·The Journal of Biological Chemistry·D RonA Gordon
Apr 8, 2000·Ophthalmic Research·P MoriartyM Boulton
Sep 27, 2001·Proceedings of the National Academy of Sciences of the United States of America·A QuattroneD L Alkon
Feb 9, 2002·The Journal of Biological Chemistry·Ilana Goldberg-CohenAndrew P Levy
Jun 11, 2002·Methods : a Companion to Methods in Enzymology·Scott A TenenbaumJack D Keene
Jan 1, 2003·Survey of Ophthalmology·Lloyd Paul Aiello
May 27, 2005·Hormone and Metabolic Research = Hormon- Und Stoffwechselforschung = Hormones Et Métabolisme·H-P Hammes
Aug 16, 2005·Proceedings of the National Academy of Sciences of the United States of America·Alessia PascaleAlessandro Quattrone
Sep 17, 2005·Circulation Research·Annika ArmulikChrister Betsholtz
Sep 26, 2006·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Marialaura AmadioAlessia Pascale
Jun 19, 2007·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Net Das Evcimen, George L King
Jun 22, 2007·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Fiorenzo Battaini, Daria Mochly-Rosen

❮ Previous
Next ❯

Citations

Jan 7, 2011·Psychopharmacology·Alessia PascaleFabio Fumagalli
Jul 26, 2008·Reviews in Endocrine & Metabolic Disorders·Sally A Madsen-Bouterse, Renu A Kowluru
Jun 16, 2011·Journal of Biomedical Science·Ling-fang HeYa-yi Hou
Jun 24, 2014·Cell & Bioscience·Xinyuan ZhangMark C Gillies
Aug 13, 2008·Expert Opinion on Investigational Drugs·M SlevinJ Krupinski
Sep 2, 2015·RNA Biology·Cecilia OseraAlessia Pascale
Jun 18, 2016·Frontiers in Physiology·Priyia PusparajahKhalid Abdul Kadir
Jul 30, 2016·Journal of Alzheimer's Disease : JAD·Nicoletta MarchesiAlessia Pascale
Jul 6, 2010·Biochemical Pharmacology·M AmadioA Pascale
Jan 29, 2016·Cells·Irina Vlasova-St Louis, Paul R Bohjanen
Mar 13, 2012·Pharmacological Reviews·E J Verspohl
Jan 9, 2017·European Heart Journal·Ruben G de BruinEric P van der Veer
Sep 8, 2021·Frontiers in Pharmacology·Claudio BucoloAlessia Pascale
Jun 19, 2010·Biochemical and Biophysical Research Communications·Sanjaya KuruppuA Ian Smith
Nov 20, 2021·The FEBS Journal·Madeleine R Smith, Guilherme Costa

❮ Previous
Next ❯

Related Concepts

Related Feeds

Arterial-Venous in Development & Disease

Arterial-venous development may play a crucial role in cardiovascular diseases. Here is the latest research.

Blood Brain Barrier

The blood brain barrier is a border that separates blood from cerebrospinal fluid. Discover the latest search on this highly selective semipermeable membrane here.