The 5-lipoxygenase pathway regulates vasculogenesis in differentiating mouse embryonic stem cells.
Cardiovasc Res
; 86(1): 37-44, 2010 Apr 01.
Article
en En
| MEDLINE
| ID: mdl-19965960
ABSTRACT
AIMS:
It is well established that leukotrienes (LTs), products of the 5-lipoxygenase (5-LO) pathway, participate in inflammatory tissue reactions and immune responses. In the present study, the impact of the 5-LO pathway on vasculogenesis of mouse embryonic stem (ES) cells was investigated. METHODS ANDRESULTS:
Immunohistochemistry studies demonstrated that 5-LO(+) cells first appeared at day 6 of embryoid body (EB) formation from ES cells. 5-LO(+)/CD68(+) as well as 5-LO(+)/CD45(+) cells were prominent at day 10 of EB differentiation. Real-time PCR and western blot analysis revealed all constituents of the 5-LO pathway. High performance liquid chromatography analyses indicated the synthesis of LTB(4) and LTD(4) in conformity with induction of the 5-LO pathway. Furthermore, Flk-1(+)/CD105(+) cells displayed calcium- (Ca(2+)) transients in response to LTB(4), whereas CD11b(+) cells responded to LTD(4). Treatment of EBs with LTB(4) and LTD(4) resulted in phosphorylation of the mitogen-activated protein kinase ERK1/2. Pharmacological inhibition of the 5-LO pathway and stable shRNA targeting of 5-LO-activating protein decreased capillary cell areas positive for PECAM-1.CONCLUSION:
Our data demonstrate that the 5-LO pathway emerges early during ES cell differentiation into cells of the myeloid lineage and that LTs play an until now unrecognized role in vascular development of ES cells.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Araquidonato 5-Lipooxigenasa
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Proteínas Portadoras
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Células Madre Embrionarias
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Proteínas de la Membrana
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Neovascularización Patológica
Idioma:
En
Año:
2010
Tipo del documento:
Article