Survival effect of PDGF-CC rescues neurons from apoptosis in both brain and retina by regulating GSK3β phosphorylation

Abstract

Platelet-derived growth factor CC (PDGF-CC) is the third member of the PDGF family discovered after more than two decades of studies on the original members of the family, PDGF-AA and PDGF-BB. The biological function of PDGF-CC remains largely to be explored. We report a novel finding that PDGF-CC is a potent neuroprotective factor that acts by modulating glycogen synthase kinase 3β (GSK3β) activity. In several different animal models of neuronal injury, such as axotomy-induced neuronal death, neurotoxin-induced neuronal injury, 6-hydroxydopamine–induced Parkinson’s dopaminergic neuronal death, and ischemia-induced stroke, PDGF-CC protein or gene delivery protected different types of neurons from apoptosis in both the retina and brain. On the other hand, loss-of-function assays using PDGF-C null mice, neutralizing antibody, or short hairpin RNA showed that PDGF-CC deficiency/inhibition exacerbated neuronal death in different neuronal tissues in vivo. Mechanistically, we revealed that the neuroprotective effect of PDGF-CC was achieved by regulating GSK3β phosphorylation and expression. Our data demonstrate that PDGF-CC is critically required for neuronal survival and may potentially be used to treat neurodegenerative diseases. Inhibition of the PDGF-CC–PDGF receptor pathway for different clinical purposes should be conducted with caution to preserve normal neuronal functions.

Vasoprotective effect of PDGF-CC mediated by HMOX1 rescues retinal degeneration

“…Second, PDGF-CC also may have a direct neuroprotective effect on retinal photoreceptor cells, which express the PDGFRs (8, 9). Indeed, we have shown previously that PDGF-CC is a potent neuronal survival factor (9). One potential issue that remains to be defined better in future studies is to investigate astrocyte activation in detail after PDGF-CC treatment, because there seems to be a tendency for increased GFAP staining in the nerve fiber layer in the PDGF-CC-treated retinae.…”

“…The PDGF family plays important roles in the vascular system (8)(9)(10)(11). PDGF-CC was the third of the four PDGF family members discovered (12,13), long after the finding of PDGF-AA and PDGF-BB.…”

“…PDGF-CC is highly expressed in the vascular system (8,14) and is produced as a secreted homodimer that binds to and activates the PDGF receptors PDGFR-α and PDGFR-β (12,15). PDGF-CC is a critical survival/protective factor for neuronal cells (8,9,16) and macrophages (17) and has been shown to be a potent angiogenic factor (10,15,(18)(19)(20).…”

Influence of Polarized Light on Vitality of Retinal Ganglion Cells in Rats With Low-Tension Glaucoma

“…Один із основних методів для візуалізації ГКС є проведення стереотаксич-них ін'єкцій 2%-го розчину барвника Fluorogold (FG, "Termofisher scientific", США) [4,5] з подальшою їх ідентифікацією за допомо гою флуоресцентної мікроскопії [6][7][8]. Ін'єкції здійснювали з використанням такого обладнання: стандартна рамка для стереотаксису, тримач для голови щура, ін-дивідуально виконаний тримач для шприца, пінцет, мікроножиці, голкотримач та шприц Гамільтона (Hamilton).…”

“…Після чого за допомогою флуоресцентної мікроскопії, можна чітко виз-начити популяцію ГКС. Як вказують автори, така ідентифікація є високоспецифічною [6][7][8].…”