Midkine regulates pleiotrophin organ-specific gene expression: Evidence for transcriptional regulation and functional redundancy within the pleiotrophin/midkine developmental gene family
Midkine regulates pleiotrophin organ-specific gene expression: Evidence for transcriptional regulation and functional redundancy within the pleiotrophin/midkine developmental gene family
复制标题
DOI：
10.1016/j.bbrc.2005.05.160
复制
发表时间：
2005-08-05
影响因子：
3.1
通讯作者：
Deuel, TF
中科院分区：
文献类型：
--
作者：
Herradon, G;Ezquerra, L;Deuel, TF
中期因子（MK）和高度相关的细胞因子多效生长因子（PTN）构成PTN/MK发育基因家族。Mk和Ptn基因对于儿茶酚胺和肾素-血管紧张素途径的正常发育以及不同胶原的合成是必需的。目前尚不清楚Ptn和MK基因是否相互调节，或者PTN和MK在发育中是否功能冗余。我们现在比较了基因缺陷型Mk-/-和Ptn -/-小鼠中Ptn和Mk的If表达水平，发现与野生型小鼠相比，Mk -/-小鼠的脊髓、背根神经节、眼、心脏、主动脉、膀胱和尿道中Pm基因表达高度显著增加，但脑、骨髓、睾丸和肺中Pm基因表达不显著增加;在Mk -/-小鼠的心脏中发现Pm表达水平的显著的相似的230倍的增加，并且在其它六个器官中发现高度显著的但较小的增加。在Ptn -/-小鼠的任何测试器官中均未检测到Mk-基因表达水平的差异。这些数据表明，MK调节Ptn基因的表达具有高度的器官特异性，这表明，PM基因的表达遵循MK基因的表达在发展中，Ptn基因表达的增加是补偿MK-/-小鼠中MK的缺乏，PTN和MK共享高度的功能冗余，MK可能是非常重要的在小鼠心脏的发展。(c)2005年爱思唯尔公司All rights reserved.
Midkine (MK) and the highly related cytokine pleiotrophin (PTN) constitute the PTN/MK developmental gene family. The Mk and Ptn genes are essential for normal development of the catecholamine and renin-angiotensin pathways and the synthesis of different collagens. It is not known whether the Ptn and Mk genes regulate each other or whether PTN and MK are functionally redundant in development. We have now compared the levels If expression of Ptn and Mk in genetically deficient Mk- -/- and Ptn -/- mice and found highly significant increases in Pm gene expression in spinal cord, dorsal root ganglia, eye, heart, aorta, bladder, and urethra, but not in brain, bone marrow, testis, and lung of Mk -/- mice compared with wild type mice; a remarkable similar to 230-fold increase in Pm expression levels was found in heart of Mk -/- mice and highly significant but lesser increases were found in six other organs. Differences in levels of Mk- gene expression in Ptn -/- mice could not be detected in any of the organs tested. The data demonstrate that MK regulates Ptn gene expression with a high degree of organ specificity, suggesting that PM gene expression follows Mk gene expression in development, that the increase in Ptn gene expression is compensatory for the absence of MK in Mk- -/- mice, that PTN and MK share a high degree of functional redundancy, and that MK may be very important in the development of heart in mouse. (c) 2005 Elsevier Inc. All rights reserved.