BioMed Research International / 2017 / Article / Tab 1

Review Article

Antiangiogenic Therapy for Diabetic Nephropathy

Table 1

Candidates of endogenous antiangiogenic factors as therapeutic agents for diabetic nephropathy.

DescriptionTarget moleculeEffect on ECsClinical use

sFlt-1Soluble form of VEGFR-1 that binds to circulating VEGF and prevents it from binding to VEGFR-2.VEGFApoptosisNone
VEGF-A165bInhibitory VEGF-A splice variant which induces insufficient phosphorylation of VEGFR-2.VEGFR-2None
TumstatinProtein fragment cleaved from type IV collagen that binds to endothelium via integrin and inhibits protein synthesis.αvβ3-integrinApoptosisNone
EndostatinProtein fragment cleaved from type XVIII collagen which acts on endothelium to suppress cell cycle genes and antiapoptotic genes.α5β1-integrin (glypicans,
in China
AngiostatinProtein fragment cleaved from plasminogen which binds to potentially many proteins to induce its apoptosis.Angiomotin and
ApoptosisUnder trial
Vasohibin-1Endothelium-derived protein that causes negative feedback response in endothelial cells stimulated by VEGF-A and promotes its survival by inducing SOD2 and Sirt1.UnknownSurvivalNone

ECs, endothelial cells; sFlt-1, soluble fms-like tyrosine kinase-1; VEGF, vascular endothelial growth factor; VEGFR-2, VEGF receptor-2; SOD2, superoxide dismutase-2; Sirt1, sirtuin-1. -A165b may attenuate endothelial survival effect of VEGF-A165, but endothelial protective effect was also reported (see text). representative molecules include surface ATP synthase, NG2 proteoglycan, c-Met, and annexin II.

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