Heparin structures in FGF-2-dependent morphological transformation of astrocytes

Fibroblast growth factor-2 (FGF-2) participates in the morphological transformation of astrocytes (stellation) during the formation of glial scars in injured brains. In the current study, we used quantitative morphometric analysis to investigate the structural requirements for heparin's enhancement of FGF-2-induced stellation of cultured cortical astrocytes. Native heparin significantly promoted FGF-2-dependent astrocytic stellation, whereas heparin hexasaccharide inhibited FGF-2-dependent stellation. Furthermore, 2-O-, 6-O-, and N-desulfated heparins were unable to promote FGF-2-dependent stellation. The stellation induced by FGF-2 or by a combination of FGF-2 and native heparin was inhibited by SU5402, an FGF receptor inhibitor. These results demonstrate that the length and sulfated position of heparin are important for its enhancement of FGF-2-dependent astrocyte stellation. In addition, our findings show that heparin oligosaccharides are useful for regulating the FGF-2-dependent astrocytic transformation.