Role of JNK in network formation of human lung microvascular endothelial cells. Am J Physiol Lung Cell Mol Physiol 2008 Apr;294(4):L676-85
Date
02/12/2008Pubmed ID
18263671Pubmed Central ID
PMC2904476DOI
10.1152/ajplung.00496.2007Scopus ID
2-s2.0-42049122785 (requires institutional sign-in at Scopus site) 18 CitationsAbstract
The signaling mechanisms in vasculogenesis and/or angiogenesis remain poorly understood, limiting the ability to regulate growth of new blood vessels in vitro and in vivo. Cultured human lung microvascular endothelial cells align into tubular networks in the three-dimensional matrix, Matrigel. Overexpression of MAPK phosphatase-1 (MKP-1), an enzyme that inactivates the ERK, JNK, and p38 pathways, inhibited network formation of these cells. Adenoviral-mediated overexpression of recombinant MKP-3 (a dual specificity phosphatase that specifically inactivates the ERK pathway) and dominant negative or constitutively active MEK did not attenuate network formation in Matrigel compared with negative controls. This result suggested that the ERK pathway may not be essential for tube assembly, a conclusion which was supported by the action of specific MEK inhibitor PD 184352, which also did not alter network formation. Inhibition of the JNK pathway using SP-600125 or l-stereoisomer (l-JNKI-1) blocked network formation, whereas the p38 MAPK blocker SB-203580 slightly enhanced it. Inhibition of JNK also attenuated the number of small vessel branches in the developing chick chorioallantoic membrane. Our results demonstrate a specific role for the JNK pathway in network formation of human lung endothelial cells in vitro while confirming that it is essential for the formation of new vessels in vivo.
Author List
Medhora M, Dhanasekaran A, Pratt PF Jr, Cook CR, Dunn LK, Gruenloh SK, Jacobs ERMESH terms used to index this publication - Major topics in bold
AnimalsCell Culture Techniques
Cells, Cultured
Collagen
Drug Combinations
Endothelium, Vascular
Enzyme Inhibitors
Flavonoids
Genes, Reporter
Green Fluorescent Proteins
Humans
Laminin
MAP Kinase Kinase 4
Microcirculation
Neovascularization, Physiologic
Proteoglycans
Pulmonary Circulation
