Fibulin-1 Binds to Fibroblast Growth Factor 8 with High Affinity

Abstract

Fibulin-1 (FBLN1) is a member of a growing family of extracellular matrix glycoproteins that includes eight members and is involved in cellular functions such as adhesion, migration, and differentiation. FBLN1 has also been implicated in embryonic heart and valve development and in the formation of neural crestderived structures, including aortic arch, thymus, and cranial nerves. Fibroblast growth factor 8 (FGF8) is a member of a large family of growth factors, and its functions include neural crest cell (NCC) maintenance, specifically NCC migration as well as patterning of structures formed from NCC such as outflow tract and cranial nerves. In this report, we sought to investigate whether FBLN1 and FGF8 have cooperative roles in vivo given their influence on the development of the same NCC-derived structures. Surface plasmon resonance binding data showed that FBLN1 binds tightly to FGF8 and prevents its enzymatic degradation by ADAM17.

Fibroblast growth factor inducedUcp1expression in preadipocytes requires PGE2 biosynthesis and glycolytic flux

“…In fact, one FGF8-binding protein present in preadipocytes is Fibulin-1, which has been shown to sequester FGF8, thereby suppressing FGF signaling. 40 Expression levels of Fibulin-1 were indeed significantly higher in control and FGF1 treated preadipocytes than in FGF8b or FGF9 treated preadipocytes according to our transcriptomic data, potentially reducing FGF1 signaling activity. This highlights the potential role of FGF-binding molecules, heparin included, in modulating FGF signaling activity.…”

Murine embryos exposed to human endometrial MSCs-derived extracellular vesicles exhibit higher VEGF/PDGF AA release, increased blastomere count and hatching rates

“…Our preliminary proteomic analyses of the EV-endMSCs have revealed a wide range of proteins closely related to embryo development and implantation (manuscript in preparation). As an example, transferrin [ 39 ], vinculin [ 40 ], and fibronectin [ 41 , 42 ] have been demonstrated to promote embryo development being essential in the early embryo development and survival. Thus, EV-endMSC could be promoting embryo blastomere division and hatching by the specific protein cargo released to the embryo culture medium.…”

Role of Fibulins in Embryonic Stage Development and Their Involvement in Various Diseases

“…During the development of the cardiac outflow tract, fibulin-1 is expressed at the endothelial mesenchymal transition area, and averts the hypercellularity of the proximal endocardial cushion by conquering the outflow tract transition and the aggregation of blood cells [ 28 ]. Fibulin-1 interacts with fibroblast growth factor 8 during the development of the embryo, and maintains the neural crest cells (NCCs) and embryo survival [ 29 ]. The in vitro study on the expression analysis of fibulin-1 and fibulin-2 in the human corneal fibroblast cells using microarray revealed the expression of both of these two genes along with their binding partners, such as fibronectin, nidogen-1, aggrecan, fibrilin-1, endostatin, laminin alpha-2 chain, and ADAMTS-1 (a disintegrin and metalloproteinase with thrombospondin motif 1) metalloprotease [ 30 ].…”