Reactive oxygen species, PKC-β₁, and PKC-ζ mediate high-glucose-induced vascular endothelial growth factor expression in mesangial cells

Abstract

IG, Whiteside CI. Reactive oxygen species, PKC-␤ 1, and PKCmediate high-glucose-induced vascular endothelial growth factor expression in mesangial cells.

High glucose activates PKC-ζ and NADPH oxidase through autocrine TGF-β1 signaling in mesangial cells

“…DMEM, FBS, myristoylated PKC-pseudosubstrate peptide inhibitor (ZI) (myr-SIYRRGARRWRKL), p22 phox phosphorothioate antisense oligonucleotides (5Ј-GAT CTG CCC CAT GGT GAG GAC C-3Ј), and polyclonal antibodies against p22 phox , PKC-␤1, PKC-, Akt, and phospho-Akt Ser473 were obtained as previously described (26,63,64). Smad2/3 antibodies were purchased from Cell Signaling Technology (Beverly, MA).…”

“…We previously reported that primary cultured rat mesangial cells express predominantly PKC-with little or undetectable PKC-. PKC-activation is obligatory for high glucose-mediated increases in vascular endothelial growth factor and collagen IV expression in mesangial cells (26,64).…”

Redox Control of Renal Function and Hypertension

“…Furthermore, PKC-ë mediates high glucose-induced stimulation of NAD(P)H oxidase and F-actin disassembly; this is reversed with antisense RNAi to p22 phox and p47 phox (171). Last, PKCand PKC-␤1 mediate high glucose-induced VEGF expression, and this increase was reversed with tempol, PKC-, and PKC-␤1 inhibition (372).…”

Drugs for Diabetic Nephropathy- Full Review

“…c) It also interfere with arachidonic acid metabolism ANTI SENSE OLIGONUCLEOTIDE DIRECTED p22 (phox) [19] Vascular Endothelial growth factor (VEGF) is implicated in development of proteinuria in diabetic nephropathy. Overexpression of p22 is associated with enhanced VEGF in Diabetes.…”

“…[149,150] 2) Pan -VEGF TYROSINE KINASE INHIBITOR SU 5416-ameliorate diabetic albuminuria. [151] 3) VEGF can be blocked by using TEMPOL [19] 4) Overexpression p22 (phox) enhances VEGF directing antisense oligonucleotide will decrease VEGF. [19] Several studies are carried out with VEGF inhibitor in diabetic retinopathy and more studies are needed to determine the potency of VEGF inhibitors in renal disease.…”