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| IJCEM Copyright © 2008-All rights reserved. Published by e-Century Publishing Corporation, Madison, WI 53711 |
Int J Clin Exp Med 2011;4(4):241-251
Original Article
Post-transcriptional regulation of PDGF alpha-receptor in O-2A progenitor cells
Haiying Li, Chiayeng Wang
Center for Molecular Biology of Oral Diseases; Department of Oral Biology, University of Illinois at Chicago, Chicago, IL 60612, USA.
Received September 6, 2011; accepted September 28, 2011; Epub October 12, 2011; Published November 30, 2011
Abstract: Platelet-derived growth factor alpha-receptor (PDGFαR) mediated signaling plays a key role in the development of glial cells
of the central nervous system. In vivo and in vitro studies show that PDGFαR is actively expressed in proliferative and motile
oligodendrocyte type-2 astrocyte (O-2A) glial progenitor cells. However, PDGFαR expression is barely detectable in mature glial cells.
The exact mechanism underlying the loss of PDGFαR expression is unknown. In this study, we employed a rat brain-derived O-2A glial
progenitor cell line, CG4 as a culture model to investigate signals capable of inhibiting PDGFαR gene expression. PDGFαR mRNA
levels decreased significantly as CG4 cells differentiated into both oligodendrocyte and astrocyte lineages. We showed that inhibition of
PDGFαR expression was promoted by prostaglandin E2 via protein kinase A activation. Both cAMP analogs (db-cAMP and 8’bromo-
cAMP) and adenylate cyclase activator (forskolin) were potent suppressors of PDGFαR expression in CG4 cells. This inhibitory effect
resulted from an increased destabilization of PDGFαR mRNA instead of a decreased PDGFαR gene transcription. Importantly, db-
cAMP failed to reduce PDGFαR mRNA levels in several PDGFαR over-expressing human glioma cell lines. Together, these results
suggest that cAMP-dependent pathway played a key regulatory role in controlling PDGFαR mRNA levels during normal glial
development, and that a breakdown in the cross talk between cAMP and PDGF pathways may underlie the uncontrolled proliferation
and immature differentiation state in the glial tumors. (IJCEM1109002).
Key words: PDGF, cyclic AMP, mRNA turnover, glioma
Full Text PDF
Address all correspondence to:
Dr. Chiayeng Wang
Center for Molecular Biology of Oral Diseases
801 South Paulina Street
University of Illinois at Chicago
Chicago, IL 60612
Phone: 312-996-4530
Fax: 312-413-1604
E-mail: chiayeng@uic.edu
Original Article
Post-transcriptional regulation of PDGF alpha-receptor in O-2A progenitor cells
Haiying Li, Chiayeng Wang
Center for Molecular Biology of Oral Diseases; Department of Oral Biology, University of Illinois at Chicago, Chicago, IL 60612, USA.
Received September 6, 2011; accepted September 28, 2011; Epub October 12, 2011; Published November 30, 2011
Abstract: Platelet-derived growth factor alpha-receptor (PDGFαR) mediated signaling plays a key role in the development of glial cells
of the central nervous system. In vivo and in vitro studies show that PDGFαR is actively expressed in proliferative and motile
oligodendrocyte type-2 astrocyte (O-2A) glial progenitor cells. However, PDGFαR expression is barely detectable in mature glial cells.
The exact mechanism underlying the loss of PDGFαR expression is unknown. In this study, we employed a rat brain-derived O-2A glial
progenitor cell line, CG4 as a culture model to investigate signals capable of inhibiting PDGFαR gene expression. PDGFαR mRNA
levels decreased significantly as CG4 cells differentiated into both oligodendrocyte and astrocyte lineages. We showed that inhibition of
PDGFαR expression was promoted by prostaglandin E2 via protein kinase A activation. Both cAMP analogs (db-cAMP and 8’bromo-
cAMP) and adenylate cyclase activator (forskolin) were potent suppressors of PDGFαR expression in CG4 cells. This inhibitory effect
resulted from an increased destabilization of PDGFαR mRNA instead of a decreased PDGFαR gene transcription. Importantly, db-
cAMP failed to reduce PDGFαR mRNA levels in several PDGFαR over-expressing human glioma cell lines. Together, these results
suggest that cAMP-dependent pathway played a key regulatory role in controlling PDGFαR mRNA levels during normal glial
development, and that a breakdown in the cross talk between cAMP and PDGF pathways may underlie the uncontrolled proliferation
and immature differentiation state in the glial tumors. (IJCEM1109002).
Key words: PDGF, cyclic AMP, mRNA turnover, glioma
Full Text PDF
Address all correspondence to:
Dr. Chiayeng Wang
Center for Molecular Biology of Oral Diseases
801 South Paulina Street
University of Illinois at Chicago
Chicago, IL 60612
Phone: 312-996-4530
Fax: 312-413-1604
E-mail: chiayeng@uic.edu
