Transcriptional profiling of gene expression patterns during sphingosine 1-phosphate-induced mesangial cell proliferation.
Transcriptional profiling of gene expression patterns during sphingosine 1-phosphate-induced mesangial cell proliferation.
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DOI：
10.1016/s0006-291x(02)02850-4
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发表时间：
2003-01
影响因子：
3.1
通讯作者：
S. Katsuma;Y. Hada;S. Shiojima;A. Hirasawa;A. Tanoue;K. Takagaki;T. Ohgi;J. Yano;G. Tsujimoto
中科院分区：
文献类型：
--
作者：
S. Katsuma;Y. Hada;S. Shiojima;A. Hirasawa;A. Tanoue;K. Takagaki;T. Ohgi;J. Yano;G. Tsujimoto
已知鞘氨醇1-磷酸（S1 P）调节细胞增殖、凋亡和运动。最近，我们报道了S1 P及其类似物二氢S1 P（DHS 1 P）促进大鼠系膜细胞增殖。为了研究S1 P和DHS 1 P诱导的系膜细胞增殖的信号转导机制，我们对系膜细胞增殖过程中的基因表达进行了cDNA微阵列分析。就整体模式而言，S1 P和DHS 1 P诱导的基因表达波与强效系膜促分裂原血小板衍生生长因子（PDGF）诱导的基因表达波相似，而我们发现了几种基因，如两种生长因子，结缔组织生长因子（CTGF）和肝素结合EGF样生长因子（HB-EGF），它们由鞘脂诱导，但不由PDGF诱导。聚类分析还发现，与S1 P刺激的细胞相比，在DHS 1 P刺激的细胞中高度表达的钙依赖性分子。钙动员分析显示，DHS 1 P比S1 P具有更高的细胞内钙动员幅度，表明S1 P和DHS 1 P差异调节细胞内钙动员，可能导致系膜细胞中不同的基因表达。大规模的基因表达监测，使我们能够确定S1 P诱导的转录特性在系膜细胞增殖。
Sphingosine 1-phosphate (S1P) is known to regulate cell proliferation, apoptosis, and motility. Recently, we have reported that S1P and its analogue dihydro-S1P (DHS1P) promote proliferation of rat cultured mesangial cells. To investigate the signaling mechanisms underlying S1P- and DHS1P-induced mesangial cell proliferation, we performed cDNA microarray analysis of gene expression during mesangial cell proliferation. In terms of the overall pattern, gene expression waves induced by S1P and DHS1P were similar to those induced by a potent mesangial mitogen platelet-derived growth factor (PDGF), whereas we found several genes, such as two growth factors, connective tissue growth factor (CTGF) and heparin-binding EGF-like growth factor (HB-EGF), which were induced by the sphingolipids, but not by PDGF. Cluster analysis also identified calcium-dependent molecules highly expressed in DHS1P-stimulated cells compared to S1P-stimulated cells. Calcium mobilization analysis showed that DHS1P had higher magnitudes of intracellular calcium mobilization than S1P, suggesting that S1P and DHS1P differentially regulate intracellular calcium mobilization, possibly leading to different gene expression in mesangial cells. The large-scale monitoring of gene expression performed here allows us to identify S1P-induced transcriptional properties during mesangial cell proliferation.