Notch signaling regulates the differentiation of bone marrow-derived cells into smooth muscle-like cells during arterial lesion formation
Notch signaling regulates the differentiation of bone marrow-derived cells into smooth muscle-like cells during arterial lesion formation
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DOI：
10.1016/j.bbrc.2009.02.116
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发表时间：
2009-04-17
影响因子：
3.1
通讯作者：
Kurabayashi, Masahiko
中科院分区：
文献类型：
--
作者：
Doi, Hiroshi;Iso, Tatsuya;Kurabayashi, Masahiko
骨髓来源的细胞可以分化为平滑肌样细胞，导致血管发病。然而，分化的分子机制仍不清楚。我们最近报道，Notch信号促进间充质细胞向SMC分化，而Notch靶点HERP1则抑制间充质细胞向SMC的分化。在BM来源的单个核细胞分化为SMA阳性细胞的过程中，Jagged1和SMC特异性Notch3的表达增加。用γ-分泌酶抑制剂阻断Notch可阻止SMA的诱导。将绿色荧光蛋白(GFP)阳性细胞移植到小鼠股动脉，造成线状血管损伤。增厚的新生内膜中可见大量GFP/Jagged1或GFP/Notch3双阳性细胞。相反，在Notch抑制因子HERP1大量表达的新生内膜中，只有少数SMA阳性细胞呈GFP阳性。结论：Notch-HERP1通路在骨髓来源的单个核细胞向SMLC分化过程中起重要作用。(C)2009 Elsevier Inc.保留所有权利
Bone marrow- (BM-) derived cells can differentiate into smooth muscle-like cells (SMLC), resulting in vascular pathogenesis. However, the molecular mechanism of the differentiation remains unknown. We have recently reported that Notch signaling promotes while a Notch target HERP1 inhibit the differentiation of mesenchymal cells to SMC. During the differentiation of BM-derived mononuclear cells into smooth muscle alpha-actin (SMA)-positive cells, expression of Jagged1 and SMC-specific Notch3 was increased. Blocking Notch with gamma-secretase inhibitor prevented the induction of SMA. Wire-mediated vascular injury was produced in femoral arteries in mice transplanted with green fluorescent protein (GFP)-positive cells. Many double-positive cells for GFP/Jagged1 or GFP/Notch3 were detected in the thickened neointima. In contrast, only a few SMA-positive cells were positive for GFP in neointima where HERP1, a suppressor for Notch, were abundantly expressed. In conclusion, Notch-HERP1 pathway plays an important role in differentiation of BM-derived mononuclear cells into SMLC. (C) 2009 Elsevier Inc. All rights reserved