Heterogeneous nuclear ribonucleoprotein-H plays a suppressive role in visceral myogenesis

Heterogeneous nuclear ribonucleoprotein-H plays a suppressive role in visceral myogenesis
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DOI:
10.1016/s0925-4773(01)00377-x
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发表时间:
2001-06-01
影响因子:
2.6
通讯作者:
Schuger, L
Schuger, L
中科院分区:
生物学4区
文献类型:
--
作者:
Liu, JH;Beqaj, S;Schuger, L

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小鼠胚胎间充质细胞在培养物中伸展/伸长时经历自发平滑肌(SM)分化(Relan等人,J. Cell Biol.147(1999)1341; Yang等人,Development 125(1998)2621; Yang等人,Development 126(1999)3027)。使用这些细胞,我们产生了一个消减cDNA文库,以确定潜在的SM肌生成抑制。差异表达的基因之一是异质核核糖核蛋白-H(hnRNP-H),其参与前体mRNA的选择性剪接,hnRNP-H在SM分化开始前的间充质细胞中高表达,但在SM肌发生的间充质细胞中其表达迅速下降。在体内,hnRNP-H表达的下降仅限于内脏SM细胞。反义寡核苷酸和反义RNA被用来抑制hnRNP-H合成在SM分化间充质细胞和胚胎肺外植体。hnRNP-H水平的降低导致SM特异性基因表达的上调和肺外植体中支气管SM发育的增加。细胞培养物中hnRNP-H过表达具有相反的效果。因此,这些研究表明hnRNP-H在控制内脏肌发生中的新作用。(C)2001爱思唯尔科学爱尔兰有限公司保留所有权利。
Mouse embryonic mesenchymal cells undergo spontaneous smooth muscle (SM) differentiation upon spreading/elongation in culture (Relan et al., J. Cell Biol. 147 (1999) 1341; Yang et al., Development 125 (1998) 2621; Yang et al., Development 126 (1999) 3027). Using these cells we generated a subtracted cDNA library to identify potential suppressors of SM myogenesis. One of the differentially expressed genes was heterogeneous nuclear ribonucleoprotein-H (hnRNP-H), which is involved in pre-mRNA alternative splicing, hnRNP-H was highly expressed in mesenchymal cells prior to the onset of SM differentiation, but its expression rapidly decreased in mesenchymal cells undergoing SM myogenesis. In vivo, the drop in hnRNP-H expression was restricted to visceral SM cells. Antisense oligodeoxynucleotide and antisense RNA were used to inhibit hnRNP-H synthesis in SM-differentiating mesenchymal cells and in embryonic lung explants. A decrease in hnRNP-H levels resulted in upregulation of SM-specific gene expression and increased bronchial SM development in lung explants. hnRNP-H overexpression in cell cultures had the opposite effect. These studies, therefore, indicate a novel role for hnRNP-H in the control of visceral myogenesis. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.