Zádor Erno
Institute of Biochemistry, Faculty of Medicine, University of Szeged, Szeged, Dóm tér 9, H-6720, Hungary.
Biochem Biophys Res Commun. 2008 Oct 17;375(2):265-70. doi: 10.1016/j.bbrc.2008.08.024. Epub 2008 Aug 14.
Ras and calcineurin are members of two independent pathways in muscle growth but their interaction is not known. This work shows that the transfection of about 1% of the muscle fibers with dominant negative Ras (dnRas) shows a wilder effect; it stimulates the fiber growth in the entire regenerating soleus muscle, including the nontransfected fibers. Co-transfection with the calcineurin inhibitor cain/cabin prevented the growth stimulation. Injection of antibody for interleukin-4 (IL-4) also abolished the growth ameliorating effect. These results suggest that the inactivation of Ras in 1% of the fibers upregulates the calcineurin-NFAT-IL-4 pathway and the secreted IL-4 triggers fiber growth stimulation in the whole regenerating soleus muscle of the rat. The results highlight the importance of the autocrine-paracrine regulation in muscle regeneration and hint to a novel method of gene theraphy of degenerative-regenerative muscle dystrophies.
Ras和钙调神经磷酸酶是肌肉生长中两条独立信号通路的成员，但它们之间的相互作用尚不清楚。这项研究表明，用显性负性Ras（dnRas）转染约1%的肌纤维会产生更广泛的效应；它能刺激整个再生比目鱼肌中的纤维生长，包括未转染的纤维。与钙调神经磷酸酶抑制剂cain/cabin共转染可阻止生长刺激。注射白细胞介素-4（IL-4）抗体也消除了生长改善效应。这些结果表明，1%的纤维中Ras失活会上调钙调神经磷酸酶-NFAT-IL-4信号通路，分泌的IL-4会触发大鼠整个再生比目鱼肌中的纤维生长刺激。这些结果突出了自分泌-旁分泌调节在肌肉再生中的重要性，并提示了一种治疗退行性-再生性肌肉营养不良的新基因治疗方法。
