Sca-1 expression is required for efficient remodeling of the extracellular matrix during skeletal muscle regeneration.
Sca-1 expression is required for efficient remodeling of the extracellular matrix during skeletal muscle regeneration.
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DOI：
10.1016/j.ydbio.2008.10.036
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发表时间：
2009-02-01
影响因子：
2.7
通讯作者：
Pavlath, Grace K.
中科院分区：
文献类型：
--
作者：
Kafadar, Kimberly A.;Yi, Lin;Ahmad, Yusra;So, Leslie;Rossi, Fabio;Pavlath, Grace K.
Sca-1（干细胞抗原-1）是Ly-6家族蛋白的成员，其在多种组织中的细胞生长、分化和自我更新中起作用。在骨骼肌中，Sca-1负调节成肌细胞增殖和分化，并可能在祖细胞的维持中起作用。我们研究了Sca-1在骨骼肌再生中的作用，并在这里显示，Sca-1的表达在肌肉损伤后的肌源性细胞亚群中上调。我们证明，从破碎的肌肉提取物上调Sca-1在体外成肌细胞的表达，这种效果是可逆的，独立于细胞增殖。Sca-1-/-小鼠表现出肌肉再生缺陷，损伤后纤维化发展。Sca-1-/-肌肉显示基质金属蛋白酶活性降低，基质金属蛋白酶是细胞外基质重塑的关键调节因子。有趣的是，我们发现卫星细胞的数量在野生型和Sca-1-/-肌肉中是相似的，这表明在卫星细胞中Sca-1在自我更新中不起作用。我们推测Sca-1直接或间接上调基质金属蛋白酶的活性，导致基质分解和有效的肌肉再生。进一步阐明Sca-1在基质重塑中的作用可能有助于开发治疗纤维化疾病的新治疗策略。
Sca-1 (Stem Cell Antigen-1) is a member of the Ly-6 family proteins that functions in cell growth, differentiation, and self-renewal in multiple tissues. In skeletal muscle Sca-1 negatively regulates myoblast proliferation and differentiation, and may function in the maintenance of progenitor cells. We investigated the role of Sca-1 in skeletal muscle regeneration and show here that Sca-1 expression is upregulated in a subset of myogenic cells upon muscle injury. We demonstrate that extract from crushed muscle upregulates Sca-1 expression in myoblasts in vitro, and that this effect is reversible and independent of cell proliferation. Sca-1-/- mice exhibit defects in muscle regeneration, with the development of fibrosis following injury. Sca-1-/- muscle displays reduced activity of matrix metalloproteinases, critical regulators of extracellular matrix remodeling. Interestingly, we show that the number of satellite cells is similar in wild-type and Sca-1-/- muscle, suggesting that in satellite cells Sca-1 does not play a role in self-renewal. We hypothesize that Sca-1 upregulates, directly or indirectly, the activity of matrix metalloproteinases, leading to matrix breakdown and efficient muscle regeneration. Further elucidation of the role of Sca-1 in matrix remodeling may aid in the development of novel therapeutic strategies for the treatment of fibrotic diseases.
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影响因子：
7.8
作者：
Asakura, Atsushi;Seale, Patrick;Girgis-Gabardo, Adele;Rudnicki, Michael A
通讯作者：
Rudnicki, Michael A
影响因子：
5.5
作者：
Bondesen, BA;Mills, ST;Pavlath, GK
通讯作者：
Pavlath, GK
影响因子：
4.3
作者：
Chen, HC;Frissora, F;Muthusamy, N
通讯作者：
Muthusamy, N
DOI：
10.1073/pnas.1036475100
发表时间：
2003-05-13
影响因子：
11.1
作者：
Bonyadi, M;Waldman, SD;Stanford, WL
通讯作者：
Stanford, WL
影响因子：
5.5
作者：
Bondesen, BA;Mills, ST;Pavlath, GK
通讯作者：
Pavlath, GK