Skeletal muscle-derived progenitors capable of differentiating into cardiomyocytes proliferate through myostatin-independent TGF-β family signaling
Skeletal muscle-derived progenitors capable of differentiating into cardiomyocytes proliferate through myostatin-independent TGF-β family signaling
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DOI：
10.1016/j.bbrc.2007.11.087
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发表时间：
2008-01-25
影响因子：
3.1
通讯作者：
Oh, Hidemasa
中科院分区：
文献类型：
--
作者：
Nomura, Tetsuya;Ueyama, Tomomi;Oh, Hidemasa
骨骼肌源性干细胞（MDSC）的存在已被建议在哺乳动物中，然而，控制MDSC增殖的信号通路仍然在很大程度上未知。在这里，我们报告的分离肌球衍生祖细胞（MDPC），可以引起跳动的心肌细胞从成人骨骼肌。我们发现，卵泡抑素，TGF-β家族成员的拮抗剂，主要在MDPC中表达，而肌生成抑制素主要在肌源性细胞和成熟骨骼肌中表达。虽然卵泡抑素通过Smad 2/3失活和细胞周期进程增强MDPC的复制生长，但肌生成抑制素的破坏并不增加MDPC的增殖。相比之下，抑制激活素A（ActA）或生长分化因子11（GDF 11）信号转导通过下调p21和增加cdk 2/4和细胞周期蛋白D1的水平显着增加MDPC增殖。因此，卵泡抑素可能是一种有效的祖细胞增强剂，中和ActA和GDF 11信号，以调节骨骼肌中MDPC的生长。(C)2007年爱思唯尔公司All rights reserved.
The existence of skeletal muscle-derived stem cells (MDSCs) has been suggested in mammals; however, the signaling pathways controlling MDSC proliferation remain largely unknown. Here we report the isolation of myosphere-derived progenitor cells (MDPCs) that can give rise to beating cardiomyocytes from adult skeletal muscle. We identified that follistatin, an antagonist of TGF-beta family members, was predominantly expressed in MDPCs, whereas myostatin was mainly expressed in myogenic cells and mature skeletal muscle. Although follistatin enhanced the replicative growth of MDPCs through Smad2/3 inactivation and cell cycle progression, disruption of myostatin did not increase the MDPC proliferation. By contrast, inhibition of activin A (ActA) or growth differentiation factor 11 (GDF11) signaling dramatically increased MDPC proliferation via down-regulation of p21 and increases in the levels of cdk2/4 and cyclin D1. Thus, follistatin may be an effective progenitor-enhancing agent neutralizing ActA and GDF11 signaling to regulate the growth of MDPCs in skeletal muscle. (C) 2007 Elsevier Inc. All rights reserved.