Fractone-heparan sulphates mediate FGF-2 stimulation of cell proliferation in the adult subventricular zone

硫酸肝素介导 FGF-2 刺激成人脑室下区细胞增殖

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作者:V Douet, A Kerever, E Arikawa-Hirasawa, F Mercier

Conclusions

Our results demonstrate that FGF-2 requires HS to stimulate cell proliferation in the SVZa and suggest that HS associated with fractones and vascular basement membranes are responsible for activating FGF-2. Therefore, fractones and vascular basement membranes may function as a HS niche to drive cell proliferation in the adult neurogenic zone.

Methods

Heparitinase-1 was intracerebroventricularly injected with FGF-2 to N-desulfate HS proteoglycans and determine whether the loss of HS and of FGF-2 binding to fractones modifies FGF-2 effect on cell proliferation. We also examined in vivo the binding of Alexa-Fluor-FGF-2 in relationship with the location of HS immunoreactivity in the SVZa.

Results

Heparatinase-1 drastically reduced the stimulatory effect of FGF-2 on cell proliferation in the SVZa. Alexa-Fluor-FGF-2 binding was strictly co-localized with HS immunoreactivity in fractones and adjacent vascular basement membranes in the SVZa. Conclusions: Our results demonstrate that FGF-2 requires HS to stimulate cell proliferation in the SVZa and suggest that HS associated with fractones and vascular basement membranes are responsible for activating FGF-2. Therefore, fractones and vascular basement membranes may function as a HS niche to drive cell proliferation in the adult neurogenic zone.

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