外力作为信号诱导基因的选择性剪接与力生长因子表达

Mechanical Signals Induced Gene Alternative Splicing and The Expression of Mechano Growth Factor

许多种类的细胞都响应力信号,人们将这些细胞称为力效应细胞(mechanocyte).应力可引起细胞在基因水平或表达水平的调控,其中胰岛素样生长因子Ⅰ(insulin-like growth factor-Ⅰ,IGFⅠ)是力学敏感因子.对骨骼肌的长期拉伸实验发现,IGF-Ⅰ不仅表达量受到拉伸刺激的调控,而且存在多种变异体形式,其中一种对力刺激敏感,只在拉伸作用下产生,命名为力生长因子(mechano growth factor,MGF).进一步研究发现,MGF能激活卫星细胞、促进成肌细胞增殖,在治疗肌损失、预防心肌损伤和修复神经损伤等方面有重要的作用.机械拉伸也可以使成骨细胞表达MGF,研究表明,对成骨细胞施加应变为15%的周期性拉伸刺激,细胞的IGFⅠ表达量增加,同时表达MGF剪接变异体.对MGF的深入研究可望在疾病治疗和组织工程修复领域取得广泛的应用.

Many kinds of cells responsing to mechanical signals were named mechanocytes, including endothelial cells, fibroblasts, osteoblasts, smooth muscle cells. Stress can cause cellular regulation in gene level, and insulin-like growth factor Ⅰ （IGF- Ⅰ） is one of the factors sensitive to mechanical stimulation. Through the mechanical stretching to skeletal muscle, it was found that mechanical stimulus led to the generation of two kinds of IGF- Ⅰisoforms, one of which was named mechano growth factor （MGF）. MGF can activate satellite cells, promote the proliferation of myoblasts, and plays an important role in treating the loss of muscle mass, preventing myocardial damage and repairing nerve damage, etc. Mechanical stretch can also cause osteoblasts to express MGF, and studies suggested that cyclic stretching （The strain rate is 15%） applied to osteoblasts increased the expression oflGF- Ⅰ and produced the splicing isoform MGF. The further study on MGF may broad prospects for treating diseases and tissue engineering.