Linked Life Data

11259389

Source:http://linkedlifedata.com/resource/pubmed/id/11259389

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2001-3-22
pubmed:abstractText
In previous studies, added parathyroid hormone-related protein (PTHrP) inhibits whereas transfected PTHrP stimulates the proliferation of A10 aortic smooth muscle cells by nuclear translocation of the peptide. In the present studies, we asked whether these paradoxical trophic actions of PTHrP occur in smooth muscle cells (SMC) cultured from small intrarenal arteries of, and whether they are altered in, 12-wk-old spontaneously hypertensive rats (SHR) as compared to normotensive Wistar-Kyoto (WKY) rats. SHR cells grew faster than WKY cells. PTHrP transcript was increased in SHR-derived cells whereas PTH1 receptor (PTH1R) transcripts were similar in both cell lines. In both strains of cells, stable transfection with human PTHrP(1-139) cDNA did not further induce proliferation, suggesting maximal effect of endogenous PTHrP in wild cells. In contrast, transfection with antisense hPTHrP(1-139) cDNA, which abolished PTHrP mRNA, decreased WKY but increased SHR cell proliferation. Added PTHrP(1-36) (1-100 pM) decreased WKY and increased SHR cell proliferation. Additional studies indicated that the preferential coupling of PTH1-R to G-protein Gi was responsible for the proliferative effect of exogenous PTHrP in SHR cells. Moreover, PTHrP was detected in the nucleolus of a fraction of WKY and SHR renal SMC, in vitro as well as in situ, suggesting that the nucleolar translocation of PTHrP might be involved in the proliferative effects of endogenous PTHrP. In renovascular SMC, added PTHrP is antimitogenic, whereas endogenously produced PTHrP is mitogenic. These paradoxical effects of PTHrP on renovascular SMC proliferation appear to be reversed in the SHR model of genetic hypertension. A new concept emerges from these results, according to which a single molecule may have opposite effects on VSMC proliferation under physiological and pathophysiological conditions.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0892-6638
pubmed:author
pubmed:issnType
Print
pubmed:volume
15
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
707-18
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:11259389-Animals, pubmed-meshheading:11259389-Arteries, pubmed-meshheading:11259389-Blotting, Western, pubmed-meshheading:11259389-Cell Division, pubmed-meshheading:11259389-Cells, Cultured, pubmed-meshheading:11259389-Cholera Toxin, pubmed-meshheading:11259389-Cloning, Molecular, pubmed-meshheading:11259389-Disease Models, Animal, pubmed-meshheading:11259389-Humans, pubmed-meshheading:11259389-Hypertension, pubmed-meshheading:11259389-Immunohistochemistry, pubmed-meshheading:11259389-Kidney, pubmed-meshheading:11259389-Male, pubmed-meshheading:11259389-Muscle, Smooth, Vascular, pubmed-meshheading:11259389-Parathyroid Hormone-Related Protein, pubmed-meshheading:11259389-Proteins, pubmed-meshheading:11259389-Rats, pubmed-meshheading:11259389-Rats, Inbred SHR, pubmed-meshheading:11259389-Rats, Inbred WKY, pubmed-meshheading:11259389-Receptor, Parathyroid Hormone, Type 1, pubmed-meshheading:11259389-Receptors, Parathyroid Hormone, pubmed-meshheading:11259389-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:11259389-Transfection, pubmed-meshheading:11259389-Virulence Factors, Bordetella
pubmed:year
2001
pubmed:articleTitle
Paradoxical actions of exogenous and endogenous parathyroid hormone-related protein on renal vascular smooth muscle cell proliferation: reversion in the SHR model of genetic hypertension.
pubmed:affiliation
Section of Renovascular Pharmacology and Physiology (INSERM-ULP), University Louis Pasteur School of Medicine, Strasbourg, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't