Armand Anne-Sophie, Launay Thierry, Pariset Claude, Della Gaspera Bruno, Charbonnier Frédéric, Chanoine Christophe
Laboratoire de Biologie du Développement et de la Différenciation Neuromusculaire, LNRS UMR 7060, Centre Universitaire des Saints-Pères, Université René Descartes, 45 rue des Saints-Pères, F-75720 Paris Cedex 06, France.
Biochim Biophys Acta. 2003 Sep 23;1642(1-2):97-105. doi: 10.1016/s0167-4889(03)00103-4.
FGF6, a member of the fibroblast growth factor (FGF) family, accumulated almost exclusively in the myogenic lineage, supporting the finding that FGF6 could specifically regulate myogenesis. Using FGF6 (-/-) mutant mice, important functions in muscle regeneration have been proposed for FGF6 but remain largely controversial. Here, we examined the effect of a single injection of recombinant FGF6 (rhFGF6) on the regeneration of mouse soleus subjected to cardiotoxin injection, specifically looking for molecular and morphological phenotypes. The injection of rhFGF6 has two effects. First, there is an up-regulation of cyclin D1 mRNA, accounting for the regulating role of a high FGF6 concentration on proliferation, and second, differentiation markers such as CdkIs and MHC I and Tn I increase and cellular differentiation is accelerated. We also show a down-regulation of endogenous FGF6, acceleration of FGFR1 receptor expression and deceleration of the FGFR4 receptor expression, possibly accounting for biphasic effects of exogenous FGF6 on muscle regeneration.
成纤维细胞生长因子6（FGF6）是成纤维细胞生长因子（FGF）家族的一员，几乎仅在肌源性谱系中积累，这支持了FGF6可特异性调节肌生成的发现。利用FGF6基因敲除（-/-）突变小鼠，已提出FGF6在肌肉再生中具有重要功能，但在很大程度上仍存在争议。在此，我们研究了单次注射重组FGF6（rhFGF6）对经心脏毒素注射的小鼠比目鱼肌再生的影响，特别关注分子和形态学表型。注射rhFGF6有两个作用。第一，细胞周期蛋白D1 mRNA上调，这解释了高浓度FGF6对增殖的调节作用；第二，细胞周期蛋白依赖性激酶抑制因子（CdkIs）、肌球蛋白重链I（MHC I）和肌钙蛋白I（Tn I）等分化标志物增加，细胞分化加速。我们还发现内源性FGF6下调、FGFR1受体表达加速以及FGFR4受体表达减速，这可能解释了外源性FGF6对肌肉再生的双相作用。
