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

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 i...

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Autores principales: Tang, Zhongshu, Arjunan, Pachiappan, Lee, Chunsik, Li, Yang, Kumar, Anil, Hou, Xu, Wang, Bin, Wardega, Piotr, Zhang, Fan, Dong, Lijin, Zhang, Yongqing, Zhang, Shi-Zhuang, Ding, Hao, Fariss, Robert N., Becker, Kevin G., Lennartsson, Johan, Nagai, Nobuo, Cao, Yihai, Li, Xuri
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2856029/
https://www.ncbi.nlm.nih.gov/pubmed/20231377
http://dx.doi.org/10.1084/jem.20091704
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author Tang, Zhongshu
Arjunan, Pachiappan
Lee, Chunsik
Li, Yang
Kumar, Anil
Hou, Xu
Wang, Bin
Wardega, Piotr
Zhang, Fan
Dong, Lijin
Zhang, Yongqing
Zhang, Shi-Zhuang
Ding, Hao
Fariss, Robert N.
Becker, Kevin G.
Lennartsson, Johan
Nagai, Nobuo
Cao, Yihai
Li, Xuri
author_facet Tang, Zhongshu
Arjunan, Pachiappan
Lee, Chunsik
Li, Yang
Kumar, Anil
Hou, Xu
Wang, Bin
Wardega, Piotr
Zhang, Fan
Dong, Lijin
Zhang, Yongqing
Zhang, Shi-Zhuang
Ding, Hao
Fariss, Robert N.
Becker, Kevin G.
Lennartsson, Johan
Nagai, Nobuo
Cao, Yihai
Li, Xuri
author_sort Tang, Zhongshu
collection PubMed
description 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.
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spelling pubmed-28560292010-10-12 Survival effect of PDGF-CC rescues neurons from apoptosis in both brain and retina by regulating GSK3β phosphorylation Tang, Zhongshu Arjunan, Pachiappan Lee, Chunsik Li, Yang Kumar, Anil Hou, Xu Wang, Bin Wardega, Piotr Zhang, Fan Dong, Lijin Zhang, Yongqing Zhang, Shi-Zhuang Ding, Hao Fariss, Robert N. Becker, Kevin G. Lennartsson, Johan Nagai, Nobuo Cao, Yihai Li, Xuri J Exp Med Article 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. The Rockefeller University Press 2010-04-12 /pmc/articles/PMC2856029/ /pubmed/20231377 http://dx.doi.org/10.1084/jem.20091704 Text en © 2010 The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Article
Tang, Zhongshu
Arjunan, Pachiappan
Lee, Chunsik
Li, Yang
Kumar, Anil
Hou, Xu
Wang, Bin
Wardega, Piotr
Zhang, Fan
Dong, Lijin
Zhang, Yongqing
Zhang, Shi-Zhuang
Ding, Hao
Fariss, Robert N.
Becker, Kevin G.
Lennartsson, Johan
Nagai, Nobuo
Cao, Yihai
Li, Xuri
Survival effect of PDGF-CC rescues neurons from apoptosis in both brain and retina by regulating GSK3β phosphorylation
title Survival effect of PDGF-CC rescues neurons from apoptosis in both brain and retina by regulating GSK3β phosphorylation
title_full Survival effect of PDGF-CC rescues neurons from apoptosis in both brain and retina by regulating GSK3β phosphorylation
title_fullStr Survival effect of PDGF-CC rescues neurons from apoptosis in both brain and retina by regulating GSK3β phosphorylation
title_full_unstemmed Survival effect of PDGF-CC rescues neurons from apoptosis in both brain and retina by regulating GSK3β phosphorylation
title_short Survival effect of PDGF-CC rescues neurons from apoptosis in both brain and retina by regulating GSK3β phosphorylation
title_sort survival effect of pdgf-cc rescues neurons from apoptosis in both brain and retina by regulating gsk3β phosphorylation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2856029/
https://www.ncbi.nlm.nih.gov/pubmed/20231377
http://dx.doi.org/10.1084/jem.20091704
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