Selective Expression and Processing of Biglycan during Migration of Bovine Aortic Endothelial Cells

Abstract

Repair of the vascular lumenal surface after injury requires a controlled endothelial cell response that includes cell migration, proliferation, and remodeling of the extracellular matrix. These cellular processes are modulated by growth factors that are released or activated following cell injury. When endothelial cell migration is stimulated in response to monolayer wounding in vitro, cells increase synthesis of small leucine-rich dermatan sulfate proteoglycans (PGs) (Kinsella, M. G., and Wight, T. N. (1986) J. Cell Biol. 102, 679-687). However, the identity of the PGs that are increased during cell migration and the factors that affect this modulation have not been identified. We now report that basic fibroblast growth factor (bFGF) is responsible for the transient increase of [35S]sulfate incorporation into PGs following monolayer wounding. SDS-polyacrylamide gel electrophoresis analysis revealed that bFGF-treated and wounded cultures increase both biglycan core protein synthesis and biglycan proteolytic processing, which results in the accumulation of a approximately 20-kDa N-terminal biglycan fragment in the culture media. Biglycan RNA steady-state levels also selectively increase 2- to 3-fold after wounding or bFGF treatment. Finally, immunocytochemical staining localizes biglycan to the tips and edges of lamellopodia on migrating cells, indicating that biglycan is found at loci at which the formation and dissolution of adhesion plaques occurs, consistent with hypotheses that predict involvement of biglycan in the control of cell migration. Taken together, these results suggest that release of endogenous bFGF is primarily responsible for altered biglycan expression, synthesis, and proteolytic processing as endothelial cells migrate after wounding.

Gene expression profiling of advanced ovarian cancer: characterization of a molecular signature involving fibroblast growth factor 2

“…The gene list defined herein also included several members of the FGF2 signaling pathway, which are known to be expressed in ovarian and EOC cells (Crickard et al, 1994;Di Blasio et al, 1995;Valve et al, 2000), and several other genes regulated by FGF2 in various contexts: CDH11 is specifically regulated by FGF2 in models of kidney fibrosis (Strutz et al, 2002), LUM expression is induced by FGF2 in keratocytes of the corneal stroma (Long et al, 2000), while BGN is similarly controlled in aortic endothelial cells (Kinsella et al, 1997). Coexpression of the latter molecules could also be related to the evidence that FGF family members bind to heparan sulfate proteoglycans of the ECM, with such interaction comprising part of the regulation of the FGF signaling unit (Plotnikov et al, 1999;Plotnikov et al, 2000;Schlessinger et al, 2000).…”

“…The largest functional category clearly contained numerous genes encoding structural proteins of the ECM (such as collagens and proteoglycans) and genes involved in cell adhesion and signaling. Notably, this list of genes also contained fibroblast growth factor 2 (FGF2), fibroblast growth factor receptor 4 (FGFR4), as well as other ECM-related genes reported to be regulated by FGF2 in various cellular contexts: OB cadherin (CDH11) (Strutz et al, 2002), lumican (LUM) (Long et al, 2000), biglycan (BGN) (Kinsella et al, 1997). At least two other functional categories were identified within the retrieved gene list, that is, several genes associated with the immune/inflammatory response of the host and various genes involved in transcription regulation (Supplementary section c), although they were not significant in terms of GO-terms distribution.…”

Regulation of Biglycan Gene Expression by Transforming Growth Factor-β Requires MKK6-p38 Mitogen-activated Protein Kinase Signaling Downstream of Smad Signaling

“…EMT involves an increase in tumor cell migration, invasion, and scattering (34). Interestingly, up-regulation of BGN (28,29) and p38 activation (61) have independently been implicated in cellular migration and adhesion. The realization that the synthesis of BGN, like fibronectin (39), is induced by TGF-␤ via p38 may thus point to an important role of this proteoglycan in tumor spread and metastasis and may contribute to the tumor-promoting effect of TGF-␤ in later stages of carcinogenesis (62).…”

“…BGN can be considered a marker gene for TGF-␤ activity that is reflected in vivo by the close spatial and temporal association of both proteins under physiological and various pathophysiological conditions. BGN has been implicated in the regulation of matrix assembly, cellular adhesion (28), migration (29), and growth factor, e.g. TGF-␤, activity (30).…”

Retrovirally Mediated Expression of Decorin by Macrovascular Endothelial Cells

“…The principal dermatan sulfate PG that is synthesized by confluent cultured aortic endothelial cells is the decorin-related PG, biglycan (21,22), consistent with immunochemical and in situ hybridization studies of endothelia in vessels (23,24). The induction of the synthesis and turnover of biglycan, but not of decorin, is regulated by the release of fibroblast growth factor-2 from endothelial cells in wounded monolayers (25). However, decorin expression, which is not detectable in monolayers of aortic endothelial cells (22), is induced in concert with type I collagen and biglycan when cells undergo sprouting and tube formation in vitro (26).…”