Sökning: id:"swepub:oai:prod.swepub.kib.ki.se:118168863" >
PDGF-DD, a novel me...
PDGF-DD, a novel mediator of smooth muscle cell phenotypic modulation, is upregulated in endothelial cells exposed to atherosclerosis-prone flow patterns
-
Thomas, JA (författare)
-
Deaton, RA (författare)
-
Hastings, NE (författare)
-
visa fler...
-
Shang, YT (författare)
-
Moehle, CW (författare)
-
- Eriksson, U (författare)
- Karolinska Institutet
-
Topouzis, S (författare)
-
Wamhoff, BR (författare)
-
Blackman, BR (författare)
-
Owens, GK (författare)
-
visa färre...
-
(creator_code:org_t)
- American Physiological Society, 2009
- 2009
- Engelska.
-
Ingår i: American journal of physiology. Heart and circulatory physiology. - : American Physiological Society. - 0363-6135 .- 1522-1539. ; 296:2, s. H442-H452
- Relaterad länk:
-
https://europepmc.or...
-
visa fler...
-
http://kipublication...
-
https://doi.org/10.1...
-
visa färre...
Abstract
Ämnesord
Stäng
- Platelet-derived growth factor (PDGF)-BB is a well-known smooth muscle (SM) cell (SMC) phenotypic modulator that signals by binding to PDGF αα-, αβ-, and ββ-membrane receptors. PDGF-DD is a recently identified PDGF family member, and its role in SMC phenotypic modulation is unknown. Here we demonstrate that PDGF-DD inhibited expression of multiple SMC genes, including SM α-actin and SM myosin heavy chain, and upregulated expression of the potent SMC differentiation repressor gene Kruppel-like factor-4 at the mRNA and protein levels. On the basis of the results of promoter-reporter assays, changes in SMC gene expression were mediated, at least in part, at the level of transcription. Attenuation of the SMC phenotypic modulatory activity of PDGF-DD by pharmacological inhibitors of ERK phosphorylation and by a small interfering RNA to Kruppel-like factor-4 highlight the role of these two pathways in this process. PDGF-DD failed to repress SM α-actin and SM myosin heavy chain in mouse SMCs lacking a functional PDGF β-receptor. Importantly, PDGF-DD expression was increased in neointimal lesions in the aortic arch region of apolipoprotein C-deficient (ApoE−/−) mice. Furthermore, human endothelial cells exposed to an atherosclerosis-prone flow pattern, as in vascular regions susceptible to the development of atherosclerosis, exhibited a significant increase in PDGF-DD expression. These findings demonstrate a novel activity for PDGF-DD in SMC biology and highlight the potential contribution of this molecule to SMC phenotypic modulation in the setting of disturbed blood flow.
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
Hitta via bibliotek
Till lärosätets databas
- Av författaren/redakt...
-
Thomas, JA
-
Deaton, RA
-
Hastings, NE
-
Shang, YT
-
Moehle, CW
-
Eriksson, U
-
visa fler...
-
Topouzis, S
-
Wamhoff, BR
-
Blackman, BR
-
Owens, GK
-
visa färre...
- Artiklar i publikationen
-
American journal ...
- Av lärosätet
-
Karolinska Institutet