Pleiotrophin is a major regulator of the catecholamine biosynthesis pathway in mouse aorta.
To better understand the phenotype of pleiotrophin (PTN the protein, Ptn the gene) genetically deficient mice (Ptn -/-), we compared the transcriptional profiles of aortae obtained from Ptn -/- and wild type (WT, Ptn +/+) mice using a 14,400 gene microarray chip (Affymetrix) and confirmed the analysis of relevant genes by real time RT-PCR. We identified a dramatic upregulation of expression of tyrosine hydroxylase (TH), DOPA decarboxylase, and dopamine beta-hydroxylase in aortae of Ptn -/- mice in comparison with WT (Ptn +/+) mice. In contrast, transcripts of phenylethanolamine-N-methyltransferase, the enzyme catalyzing the conversion of norepinephrine into epinephrine, were not detected in aortae in either mouse strain. These findings suggest that Ptn gene expression has a critical role in determining the levels of expression of the enzymes of catecholamine biosynthesis in aorta and through this mechanism, PTN may regulate levels of endogenous catecholamine synthesis and potentially the vascular tone of aorta.
Ezquerra
Laura
L
Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Rd, La Jolla, CA 92037, USA.
Herradón
Gonzalo
G
Nguyen
Trang
T
Vogt
Thomas F
TF
Bronson
Roderick
R
Silos-Santiago
Inmaculada
I
Deuel
Thomas F
TF
D000818:Animals; D001011:Aorta / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D002395:Catecholamines / Q000096:biosynthesis*; D016207:Cytokines / Q000172:deficiency / Q000378:metabolism*; D004296:Dopa Decarboxylase / Q000378:metabolism*; D004299:Dopamine beta-Hydroxylase / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009097:Multienzyme Complexes; D020411:Oligonucleotide Array Sequence Analysis; D015398:Signal Transduction / Q000502:physiology; D014157:Transcription Factors / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism*
D002352:Carrier Proteins; D002395:Catecholamines; D016207:Cytokines; D009097:Multienzyme Complexes; D014157:Transcription Factors; C066845:pleiotrophin; D014446:Tyrosine 3-Monooxygenase; D004299:Dopamine beta-Hydroxylase; D004296:Dopa Decarboxylase