Increased Wnt signaling during aging alters muscle stem cell fate and increases fibrosis
Increased Wnt signaling during aging alters muscle stem cell fate and increases fibrosis
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DOI：
10.1126/science.1144090
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发表时间：
2007-08-10
期刊：
影响因子：
56.9
通讯作者：
Rando, Thomas A.
中科院分区：
文献类型：
--
作者：
Brack, Andrew S.;Conboy, Michael J.;Rando, Thomas A.
骨骼肌的再生潜力随着年龄的增长而下降，这种损伤与组织纤维化的增加有关。我们表明，肌肉干细胞（卫星细胞）从老年小鼠倾向于转换成肌纤维化的谱系，因为他们开始增殖，这种转换是由老年动物的全身环境中的因素介导的。我们还表明，这种谱系转换与老年肌源性祖细胞中经典Wnt信号通路的激活有关，并且可以被Wnt抑制剂抑制。此外，来自老年小鼠的血清中与作为Wnt受体的Frizzled蛋白家族结合的组分可能是老年细胞中Wnt信号传导升高的原因。这些结果表明，Wnt信号通路可能在组织特异性干细胞衰老和组织纤维化随年龄增加中起关键作用。
The regenerative potential of skeletal muscle declines with age, and this impairment is associated with an increase in tissue fibrosis. We show that muscle stem cells (satellite cells) from aged mice tend to convert from a myogenic to a fibrogenic lineage as they begin to proliferate and that this conversion is mediated by factors in the systemic environment of the old animals. We also show that this lineage conversion is associated with an activation of the canonical Wnt signaling pathway in aged myogenic progenitors and can be suppressed by Wnt inhibitors. Furthermore, components of serum from aged mice that bind to the Frizzled family of proteins, which are Wnt receptors, may account for the elevated Wnt signaling in aged cells. These results indicate that the Wnt signaling pathway may play a critical role in tissue-specific stem cell aging and an increase in tissue fibrosis with age.