SFRP2调控间充质干细胞（MSCs）限制瘢痕疙瘩浸润生长的机制研究

It is known that keloids have a great harm to human, and its growth mechanism is not clear. Mesenchymal stem cells contributed to keloids and tend to be of high proliferation condition, and Wnt3a and Periostin were thought important controlling protein to it. We found SFRP2 not only inhibitted cells apoptosis and dissimilation in keloids and reduced collagen synthesis in ECM, but also showed high positive expression in MSCs in local niche of keloids. At the same time, Periostin was proved for interaction proteins of SFRP2. It was recently discovered that once Wnt/β-catenin and non Wnt/β-catenin Pathways inhbited, signal of FZD receptor on MSCs surface should put down,and infiltrating expansion of Keloids were restrained. So ,we presume that SFRP2 limits infiltrating growth of Keloids by inhibiting signal pathways of Wnt3a, Periostin. This study are designed to analysis relationship among SFRP2, Wnt3a and Periostin in MSCs in tissue after collected Keloid specimen; Secondly over expression and interference virus vector of SFRP2, Wnt3a and Periostin are constructed, and then research the change of MSCs in vitro, and clarify the interaction among them on the regulation of Keloids growth; Finally, using the Keloids animal model, SFRP2 limits to Keloid growth is observed. The results is expected to provide new targets for the biologic prevention and controlling of Keloids

瘢痕疙瘩危害大，其生长机制不清。间充质干细胞促成其趋于高增殖状态，而Wnt3a、Periostin是重要调控蛋白。我们前期发现SFRP2不仅抑制瘢痕疙瘩中细胞的凋亡、减少胶原合成，而且在MSCs也高表达；同时Periostin为其相互作用蛋白。最近研究发现，一旦抑制经典及非经典Wnt通路，下调MSCs 表面FZD受体信号，能限制Keloids浸润扩展。因此推测， SFRP2通过抑制Wnt3a、Periostin信号，限制Keloids生长。本研究用人Keloids标本，探讨SFRP2与MSCs 中Wnt3a、Periostin的关系；构建SFRP2、Wnt3a及Periostin过表达与干扰病毒载体，体外研究MSCs变化，阐明三者间相互作用对Keloids生长的调控；最后利用Keloids动物模型，研究SFRP2对Keloids生长的限制。研究结果有望为Keloids的生物学防治提供新靶点