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Signals controlling the expression of PDGF

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Abstract

PDGF is an important polypeptide growth factor that plays an essential role during early vertebrate development and is associated with tissue repair and wound healing in the adult vertebrate. Moreover, PDGF is thought to play a role in a variety of pathological phenomena, such as cancer, fibrosis and atherosclerosis. PDGF is expressed as a dimer of A and/or B chains, the precursors of which are encoded by two single copy genes. Although the PDGF genes are expressed coordinately in a number of cell types, they are independently expressed in a majority of cell types. The expression of either PDGF gene can be affected by very diverse extracellular stimuli and the type of response is dependent on the cell type that is exposed to the stimulus. Expression of the PDGF chains can be modulated at every imaginable level: by regulating accessibility of the transcription start site, by varying the transcription initiation rate, by using alternative transcription start sites, by alternative splicing, by using alternative polyadenylation signals, by varying mRNA decay rates, by regulating efficiency of translation, by protein modification, and by regulating secretion. Even upon secretion, the activity of PDGF can be modulated by non-specific or specific PDGF-binding proteins. This review provides an overview of the cell types in which the PDGF genes are expressed, of the factors that are known to affect the expression of PDGF, and of the various levels at which the expression of PDGF genes can be regulated.

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Abbreviations

aFGF:

acidic fibroblast growth factor

BAECs:

bovine aortic endothelial cells

bFGF:

basic fibroblast growth factor

BHK:

baby hamster kidney

DAG:

diacylglycerol

DH:

DNase-I-hypersensitive

ECGF:

endothelial cells growth factor

EGF:

epidermal growth factor

ER:

endoplasmic reticulum

HKMECs:

human kidney microvascular endothelial cells

HMECs:

human mammary epithelial cells

HTLV:

human T-cell leukemia virus

HUVECs:

human umbilical vein endothelial cells

IFN:

interferon

IL:

interleukin

IPF:

ideopathic pulmonary fibrosis

LDL:

low density lipoprotein

LPS:

lipopolysaccharides

PDGF:

platelet-derived growth factor

PE:

phenylephrine

PKC:

protein kinase C

PNS:

peripheral nervous system

RPE:

cell, retinal pigment epithelial cells

SHS:

nuclease Sl hypersensitive site

SMCs:

smooth muscle cells

SPARC:

secreted protein, acidic and rich in cystein

SRE:

serum response element

SRF:

serum response factor

SSV:

simian sarcoma virus

TGF:

transforming growth factor

TNF:

tumor necrosis factor

TPA:

12-O-tetradecanoylphorbol 13-actetate

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  1. Department of Molecular Biology, University of Nijmegen, The Netherlands

    Ron P. H. Dirks

  2. Department of Biochemistry, University of Nijmegen, The Netherlands

    Henri P. J. Bloemers

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  1. Ron P. H. Dirks
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Dirks, R.P.H., Bloemers, H.P.J. Signals controlling the expression of PDGF. Mol Biol Rep 22, 1–24 (1995). https://doi.org/10.1007/BF00996300

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