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

Zhongshu Tang, Pachiappan Arjunan, Chunsik Lee, Yang Li, Anil Kumar, Xu Hou, Bin Wang, Piotr Wardega, Fan Zhang, Lijin Dong, Yongqing Zhang, Shi Zhuang Zhang, Hao Ding, Robert N. Fariss, Kevin G. Becker, Johan Lennartsson, Nobuo Nagai, Yihai Cao, Xuri Li

Research output: Contribution to journalArticle

78 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)867-880
Number of pages14
JournalJournal of Experimental Medicine
Volume207
Issue number4
DOIs
StatePublished - Apr 12 2010
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Tang, Z., Arjunan, P., Lee, C., Li, Y., Kumar, A., Hou, X., Wang, B., Wardega, P., Zhang, F., Dong, L., Zhang, Y., Zhang, S. Z., Ding, H., Fariss, R. N., Becker, K. G., Lennartsson, J., Nagai, N., Cao, Y., & Li, X. (2010). Survival effect of PDGF-CC rescues neurons from apoptosis in both brain and retina by regulating GSK3β phosphorylation. Journal of Experimental Medicine, 207(4), 867-880. https://doi.org/10.1084/jem.20091704