A Wnt-TGFβ2 axis induces a fibrogenic program in muscle stem cells from dystrophic mice.
A Wnt-TGFβ2 axis induces a fibrogenic program in muscle stem cells from dystrophic mice.
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DOI：
10.1126/scitranslmed.3008411
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发表时间：
2014-12-17
影响因子：
17.1
通讯作者：
Rando TA
中科院分区：
文献类型：
--
作者：
Biressi S;Miyabara EH;Gopinath SD;Carlig PM;Rando TA
我们之前已经观察到，Wnt信号在衰老过程中激活了成体肌肉干细胞（称为卫星细胞）中的纤维化程序。我们对杜氏肌营养不良症小鼠模型中的卫星细胞进行了基因标记，以跟踪疾病进展过程中它们的命运。我们观察到，与年龄匹配的对照组相比，一部分卫星细胞具有降低的生肌潜力，并显示出促纤维化基因的表达增强。通过结合体外和体内结果，我们发现转化生长因子-β2（TGFβ2）的表达是对营养不良肌肉中经典Wnt信号升高的反应，并且所导致的TGF β活性增加以自分泌或旁分泌方式影响卫星细胞的行为。事实上，体内TGF β通路的药理学抑制降低了卫星细胞的纤维化特征。这些研究揭示了营养不良肌肉中干细胞功能障碍的细胞和分子机制，并可能有助于开发更有效和更特异的预防肌肉纤维化的治疗方法。
We have previously observed that Wnt signaling activates a fibrogenic program in adult muscle stem cells, called satellite cells, during aging. We genetically labeled satellite cells in a mouse model of Duchenne muscular dystrophy to follow their fate during the progression of the disease. We observed that a fraction of satellite cells had a reduced myogenic potential and showed enhanced expression of profibrotic genes compared to age-matched controls. By combining in vitro and in vivo results, we found that expression of transforming growth factor–β2 (TGFβ2) was induced in response to elevated canonical Wnt signaling in dystrophic muscles and that the resulting increase in TGFb activity affected the behavior of satellite cells in an autocrine or paracrine fashion. Indeed, pharmacological inhibition of the TGFb pathway in vivo reduced the fibrogenic characteristics of satellite cells. These studies shed new light on the cellular and molecular mechanisms responsible for stem cell dysfunction in dystrophic muscle and may contribute to the development of more effective and specific therapeutic approaches for the prevention of muscle fibrosis.
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影响因子：
4.4
作者：
DELAPORTE, C;DAUTREAUX, B;FARDEAU, M
通讯作者：
FARDEAU, M
影响因子：
2.7
作者：
Biressi, Stefano;Bjornson, Christopher R. R.;Carlig, Poppy M. M.;Nishijo, Koichi;Keller, Charles;Rando, Thomas A.
通讯作者：
Rando, Thomas A.
影响因子：
82.9
作者：
Cohn, Ronald D.;van Erp, Christel;Dietz, Harry C.
通讯作者：
Dietz, Harry C.
影响因子：
3.3
作者：
Andreetta, Francesca;Bernasconi, Pia;Confalonieri, Paolo
通讯作者：
Confalonieri, Paolo
DOI：
10.1186/1755-1536-5-s1-s17
发表时间：
2012
期刊：
Fibrogenesis & tissue repair
影响因子：
--
作者：
Brenner DA;Kisseleva T;Scholten D;Paik YH;Iwaisako K;Inokuchi S;Schnabl B;Seki E;De Minicis S;Oesterreicher C;Taura K
通讯作者：
Taura K