Crisona N J, Allen K D, Strohman R C
Department of Molecular and Cell Biology, University of California, Berkeley 94720, USA.
J Muscle Res Cell Motil. 1998 Jan;19(1):43-51. doi: 10.1023/a:1005300426655.
Skeletal muscle has the remarkable capacity to regenerate new muscle fibres in the event of injury or disease. This capacity lies in the satellite cells, which are myogenic stem cells residing in adult muscle. While the signals that activate satellite cells to divide in vivo are not fully understood, satellite cells grown in culture respond to the mitogenic action of fibroblast growth factor (FGF). Satellite cells from the dystrophic mdx mouse are more sensitive to FGF in culture than satellite cells from normal mice. In this study we investigated the basis for this heightened sensitivity of mdx satellite cells to FGF by measuring the number and affinity of protein and heparan sulphate proteoglycan (HSPG) receptors for FGF. We found that HSPG receptors were elevated over four-fold in the mdx cells compared with cells from normal animals. We supported this observation by measuring the synthesis of heparan sulphate (HS) and chondroitin sulphate (CS) by satellite cells in culture. Mdx satellite cells synthesized approximately ten times more of these sulphated glycosaminoglycans (GAGs) than did normal cells. For muscle fibroblasts, however, we found no significant difference in the number or affinity of protein or HSPG receptors, or in the amount of sulphated GAGs synthesized, between normal and mdx cells. We propose that the increase in FGF HSPG receptors is the basis for the heightened response of mdx satellite cells to FGF in culture and may reflect exposure of the cells to growth factors in the degenerating mdx muscle.
骨骼肌具有在受伤或患病时再生新肌纤维的非凡能力。这种能力存在于卫星细胞中,卫星细胞是存在于成年肌肉中的成肌干细胞。虽然激活卫星细胞在体内分裂的信号尚未完全了解,但在培养中生长的卫星细胞对成纤维细胞生长因子(FGF)的促有丝分裂作用有反应。来自营养不良的mdx小鼠的卫星细胞在培养中比正常小鼠的卫星细胞对FGF更敏感。在本研究中,我们通过测量FGF的蛋白质和硫酸乙酰肝素蛋白聚糖(HSPG)受体的数量和亲和力,研究了mdx卫星细胞对FGF这种更高敏感性的基础。我们发现,与正常动物的细胞相比,mdx细胞中的HSPG受体升高了四倍多。我们通过测量培养中的卫星细胞硫酸乙酰肝素(HS)和硫酸软骨素(CS)的合成来支持这一观察结果。mdx卫星细胞合成的这些硫酸化糖胺聚糖(GAG)比正常细胞多大约十倍。然而,对于肌肉成纤维细胞,我们发现正常细胞和mdx细胞之间在蛋白质或HSPG受体的数量或亲和力,或合成的硫酸化GAG的量方面没有显著差异。我们提出,FGF HSPG受体的增加是mdx卫星细胞在培养中对FGF反应增强的基础,并且可能反映了细胞暴露于退化的mdx肌肉中的生长因子。