Activin a produced by ureteric bud is a differentiation factor for metanephric mesenchyme
Activin a produced by ureteric bud is a differentiation factor for metanephric mesenchyme
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DOI：
10.1097/01.asn.0000067419.86611.21
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发表时间：
2003-06-01
影响因子：
13.6
通讯作者：
Nojima, Y
中科院分区：
文献类型：
--
作者：
Maeshima, A;Yamashita, S;Nojima, Y
本研究旨在探讨激活素-卵泡抑素系统在后肾发育中的作用。器官培养系统和培养的后肾间充质细胞被用来解决这个问题。激活素A定位于输尿管芽。激活素II型受体定位于输尿管芽和后肾间质。在器官培养系统中，外源性激活素A减小了培养的后肾的大小，延迟了输尿管芽的分支，并增大了输尿管芽的尖端。采用激活素A的拮抗剂卵泡抑素来阐明内源性激活素A的作用。外源性卵泡抑素使培养的后肾组织体积增大，输尿管芽分支增多，促进输尿管芽细胞生长。通过显性失活激活素突变受体的腺病毒转染来阻断激活素信号传导模拟了卵泡抑素的作用。在培养的后肾间充质细胞中，激活素 A 促进细胞生长；相反，卵泡抑素诱导细胞凋亡。此外，激活素 A 诱导这些细胞中上皮分化标记物的表达。这些结果表明，输尿管芽产生的激活素A不仅是输尿管芽分支的重要调节因子，也是肾脏发育过程中后肾间质的分化因子。
The present study was conducted to investigate the role of the activin-follistatin system in the development of metanephros. Organ culture system and cultured metanephric mesenchymal cells were used to address this issue. Activin A was localized in ureteric bud. Activin type II receptor was localized in ureteric bud as well as metanephric mesenchyme. In an organ culture system, exogenous activin A reduced the size of cultured metanephroi, delayed ureteric bud branching, and enlarged the tips of ureteric bud. Follistatin, an antagonist of activin A was used to clarify the role of endogenous activin A. Exogenous follistatin enlarged the size of cultured meta-nephroi, increased ureteric bud branching, and promoted cell growth in ureteric bud. Blockade of activin signaling by adenoviral transfection of dominantly negative activin mutant receptor mimics the effect of follistatin. In cultured metanephric mesenchymal cells, activin A promoted cell growth; conversely, follistatin induced apoptosis. Furthermore, activin A induced the expressions of epithelial differentiation markers in these cells. These results suggest that activin A produced by ureteric bud is not only an important regulator of ureteric bud branching, but also a differentiation factor for metanephric mesenchyme during kidney development.