Specific TSC22 domain transcripts are hypertonically induced and alternatively spliced to protect mouse kidney cells during osmotic stress
Specific TSC22 domain transcripts are hypertonically induced and alternatively spliced to protect mouse kidney cells during osmotic stress
复制标题
DOI：
10.1111/j.1742-4658.2006.05569.x
复制
发表时间：
2007-01-01
期刊：
影响因子：
5.4
通讯作者：
Kultz, Dietmar
中科院分区：
文献类型：
--
作者：
Fiol, Diego F.;Mak, Sally K.;Kultz, Dietmar
我们最近从广盐罗非鱼 (Oreochromis mossambicus) 的鳃中克隆了一种新型渗透应激转录因子 1 (OSTF1)，并证明急性高渗应激会短暂增加 OSTF1 mRNA 和蛋白质丰度 [Fiol DF, Kultz D (2005) Proc Natl Acad Sci USA 102, 927-932]。在这项研究中，进行了全基因组搜索，以确定九个不同的小鼠转化生长因子（TGF）-β刺激的克隆22结构域（TSC22D）转录本，包括糖皮质激素诱导的亮氨酸拉链（GILZ），它们是OSTF1的直系同源物。这九个 TSC22D 转录本在 14 号染色体（TSC22D1，两个剪接变体）、3 号染色体（TSC22D2，四个剪接变体）、X 号染色体（TSC22D3，两个剪接变体）和 5 号染色体（TSC22D4）上的四个基因座编码。所有九种小鼠 TSC22D 转录物均在肾皮质、髓质和乳头以及 mIMCD3 细胞系中表达。在 mIMCD3 细胞中，两个 TSC22D3 转录物（包括 GILZ）会被醛固酮上调，但不会被高渗透压上调。相反，TSC22D4 在 mIMCD3 细胞中因高渗透压而稳定上调，并且与皮质相比，在肾乳头中增加。此外，所有四种 TSC22D2 转录物都会因高渗透压而短暂上调，并且在这方面类似于罗非鱼 OSTF1。所有 TSC22D2 转录物都依赖于高渗性作为其上调信号，并且对细胞渗透性渗透剂的增加没有反应。 mRNA 稳定是高渗性上调 TSC22D2 的机制。 mIMCD3 细胞中 TSC22D2-4 的过表达可提供针对渗透应激的保护，600 mOsmol.kg(-1) 3 天后细胞存活率增加 2.7 倍即可证明。基于肾细胞对醛固酮和高渗透压的不同反应，我们得出结论，小鼠 TSC22D 基因具有不同的生理功能。 TSC22D2 和 TSC22D4 参与肾细胞对高渗的适应，表明它们代表小鼠肾细胞中渗透感应信号转导的重要元件。
We recently cloned a novel osmotic stress transcription factor 1 (OSTF1) from gills of euryhaline tilapia (Oreochromis mossambicus) and demonstrated that acute hyperosmotic stress transiently increases OSTF1 mRNA and protein abundance [Fiol DF, Kultz D (2005) Proc Natl Acad Sci USA 102, 927-932]. In this study, a genome-wide search was conducted to identify nine distinct mouse transforming growth factor (TGF)-beta-stimulated clone 22 domain (TSC22D) transcripts, including glucocorticoid-induced leucine zipper (GILZ), that are orthologs of OSTF1. These nine TSC22D transcripts are encoded at four loci on chromosomes 14 (TSC22D1, two splice variants), 3 (TSC22D2, four splice variants), X (TSC22D3, two splice variants), and 5 (TSC22D4). All nine mouse TSC22D transcripts are expressed in renal cortex, medulla and papilla, and in the mIMCD3 cell line. The two TSC22D3 transcripts (including GILZ) are upregulated by aldosterone but not by hyperosmolality in mIMCD3 cells. In contrast, TSC22D4 is stably upregulated by hyperosmolality in mIMCD3 cells and increased in renal papilla compared with cortex. Moreover, all four TSC22D2 transcripts are transiently upregulated by hyperosmolality and resemble tilapia OSTF1 in this regard. All TSC22D2 transcripts depend on hypertonicity as the signal for their upregulation and are unresponsive to increases in cell-permeable osmolytes. mRNA stabilization is the mechanism for TSC22D2 upregulation by hyperosmolality. Overexpression of TSC22D2-4 in mIMCD3 cells confers protection towards osmotic stress, as evidenced by a 2.7-fold increase in cell survival after 3 days at 600 mOsmol.kg(-1). Based on variable responsiveness to aldosterone and hyperosmolality in kidney cells we conclude that mouse TSC22D genes have diverse physiological functions. TSC22D2 and TSC22D4 are involved in adaptation of renal cells to hypertonicity suggesting that they represent important elements of osmosensory signal transduction in mouse kidney cells.