RT Journal Article
T1 Microparticles released by vascular endothelial cells increase hypoxia inducible factor expression in human proximal tubular HK-2 cells
A1 Fernández Martínez, Ana Belén
A1 Valdehita Torija, Ana
A1 Carracedo Añón, Julia María
A1 Ramírez, Rafael
A1 Lucio Cazaña, Francisco Javier de
AB Microparticles are produced by vesiculation of the cell plasma membrane and serve as vectors of cell-to-cell communication. Co-culture experiments have shown that hypoxia-inducible factor-α (HIF-α)-regulated-genes are up-regulated in human renal proximal tubular HK-2 cells by endothelial cell factors which might be transported inside endothelial microparticles (EMP). Here we aimed to study in HK-2 cells the effect of EMP, produced by activated endothelial cells, on HIF-α and HIF-α-regulated vascular endothelial growth factor-A (VEGF-A). EMP, at a concentration much lower than that found in plasma, increased the expression of HIF-α/VEGF-A in a COX-2/EP2 receptor dependent manner. Since the EMP/cells ratio was ∼1/1000, we hypothesized that paracrine mediators produced by HK-2 cells amplified the initial signal. This hypothesis was confirmed by two facts which also suggested that the mediators were conveyed by particles released by HK-2 cells: (i) HIF-α was up-regulated in HK-2 cells treated with the pellet obtained from the conditioned medium of the EMP-treated HK-2 cells. (ii) In transwell experiments, EMP-treated cells increased the expression of HIF-α in untreated HK-2 cells. Interestingly, we detected these cells, particles that were released by EMP-treated HK-2 cells. Depending on the pathological context, activation of HIF-α and VEGF-A signaling in renal tissue/cells may have either beneficial or harmful effects. Therefore, our results suggest that their presence in the urinary space of EMP produced by activated endothelial cells may influence the outcome of a number of renal diseases.
PB Elsevier
SN 1357-2725
YR 2014
FD 2014-08
LK https://hdl.handle.net/20.500.14352/131825
UL https://hdl.handle.net/20.500.14352/131825
LA eng
NO Fernández-Martínez, A. B., Valdehita Torija, A., Carracedo, J., Ramirez, R., & de Lucio-Cazaña, F. J. (2014). Microparticles released by vascular endothelial cells increase hypoxia inducible factor expression in human proximal tubular HK-2 cells. The International Journal of Biochemistry & Cell Biology, 53, 334-342. https://doi.org/10.1016/j.biocel.2014.05.025
NO This work was supported by grants SAF2008-01767 and SAF2011-26838 from the Spanish Ministerio de Ciencia e Innovación, S2010/BMD-2378 from CAM-programa de Actividades I+D en Biociencias 2010, POII10-0034-0322 from the JCCLM, PI11/01536, PI12/01489 from FISS and JA0797-2010, P010-CTS-6337, P11-CTS-7352 from JA. Ana Belén Fernández-Martinez is the recipient of a post-doctoral fellowship from JCCLM. J. Carracedo was supported by a contract from FIBICO, Programa Nicolás Monardes. Conflict of interest: None declared.
NO Ministerio de Ciencia e Innovación (España)
NO Comunidad de Madrid
NO Junta de Comunidades de Castilla-La Mancha
NO Instituto de Salud Carlos III (España)
DS Docta Complutense
RD 29 mar 2026