FGFs and their receptors, in vitro and in vivo studies: new FGF receptor in the brain, FGF-1 in muscle, and the use of functional analogues of low-affinity heparin-binding growth factor receptors in tissue repair

Abstract

Several heparin-binding growth factors (HBGFs) are thought to play a key role in the natural processes of tissue homeostasis, regeneration or repair. The HBGFs are active upon release from neighbouring inflammatory or circulating cells, as well as upon release from heparan sulfate proteoglycosaminoglycans that are associated with the extracellular matrix (ECM). To better understand the physiological role of these HBGFs, we have focused our effort on studying a subset of HBGFs, namely FGF-1 and FGF-2 and their receptors. We present the purification and characterisation of a new form of heparin-binding FGF receptor from adult bovine brain (Perderiset et al., 1992). This receptor has now been purified to homogeneity. Ligand blot and cross-linking experiments performed with labeled FGF-1 or FGF-2 revealed 80-kd and 130-kd bands. Preliminary sequence information indicates that receptor is different from the receptors, FGFR-1 to -4, but it may be related the cysteine-rich-FGF receptor (CFR). We have previously shown that FGF-1, but not FGF-2, is specifically expressed in myoblastic satellite cells during the proliferating phase preceding myoblast alignment and fusion. We have now transfected primary cultures of rat myoblastic satellite cells with FGF-1 cDNA and expressed this growth factor constitutively. The transfected cells were no longer able to form myotubes. Transfection with antisense FGF-1 induced myotube formation suggesting that endogenous expression of FGF-1 is associated with myoblastic cell differentiation. Numerous studies have concluded that the ECM represents a natural reservoir for various HBGFs.(ABSTRACT TRUNCATED AT 250 WORDS)