Laminin-1 promotes angiogenesis in synergy with fibroblast growth factor by distinct regulation of the gene and protein expression profile in endothelial cells.
Laminins are widely distributed extracellular matrix proteins. Certain laminin isoforms are predominant in vascular basement membranes and may be critical in maintaining the stability of the mature vessel. On the other hand, formation of new vessels during angiogenesis requires degradation of the basement membrane, exposing the endothelial cells to other laminin isoforms in the surrounding extracellular matrix. We studied the effects of laminin-1 (LN-1) in different in vitro and in vivo models for angiogenesis. LN-1 induced angiogenesis in the chicken chorioallantoic membrane to the same extent as fibroblast growth factor-2 (FGF-2), and vascular development in embryoid bodies was stimulated in a synergistic manner by FGF-2 and LN-1. LN-1 promoted differentiation of endothelial cells in three-dimensional collagen gels, both in the absence and presence of FGF-2. Formation of tubular structures induced by LN-1 was accompanied by increased expression of Jagged-1, a marker of endothelial differentiation, and increased levels of FGF-2 and FGFR-1 transcripts. LN-1 did not regulate signal transduction pathways known to operate down stream of FGF-2. Thus, phosphorylation of ERK was detected in FGF-2- but not in LN-1-treated cells. Taken together, this suggests that laminins may play a fundamental role in angiogenesis by directly affecting gene and protein expression profiles in endothelial cells.
Dixelius
Johan
J
Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Dag Hammarskjöldsvaüg 20, S-751 85 Uppsala, Sweden.
Jakobsson
Lars
L
Genersch
Elke
E
Bohman
Svante
S
Ekblom
Peter
P
Claesson-Welsh
Lena
L
D000818:Animals; D002642:Chick Embryo; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology; D016222:Fibroblast Growth Factor 2 / Q000502:physiology*; D007797:Laminin / Q000494:pharmacology / Q000502:physiology*; D051379:Mice; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000502:physiology*; D015398:Signal Transduction
D007797:Laminin; C121346:laminin 1; D016222:Fibroblast Growth Factor 2