Changes in human bladder epithelial cell gene expression associated with interstitial cystitis or antiproliferative factor treatment
Changes in human bladder epithelial cell gene expression associated with interstitial cystitis or antiproliferative factor treatment
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DOI：
10.1152/physiolgenomics.00055.2003
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发表时间：
2003-07-07
影响因子：
4.6
通讯作者：
Zhang, JL
中科院分区：
文献类型：
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作者：
Keay, S;Seillier-Moiseiwitsch, F;Zhang, JL
从间质性膀胱炎（IC）患者中取出的膀胱上皮细胞已被证明在几个方面与移植的对照细胞不同，包括抗增殖因子（APF）的产生，某些上皮生长因子的产生和增殖速率的改变。为了更好地理解APF在IC中异常膀胱上皮细胞增殖中的作用，我们研究了用APF与模拟APF处理的正常膀胱上皮细胞中的基因表达模式，并使用微阵列分析将其与IC与正常细胞中的表达模式进行比较。用[ P-33] dCTP标记寡聚-dT引发的总细胞RNA，并与含有3，964个人基因的cDNA的GeneFilter GF 211微阵列膜（Research Genetics）杂交。在上皮细胞增殖或分化中起作用的13个基因在IC（与对照相比）和APF处理（与模拟APF处理相比）的正常膀胱上皮细胞中一致地差异表达。IC和APF处理的细胞中基因表达的一般模式表明增殖性较低的表型，E-钙粘蛋白、磷酸核糖焦磷酸合成酶相关蛋白39和SWI/SNF复合物170-kDa亚基的表达增加，波形蛋白、α 2-整合素、α 1-连环蛋白、细胞周期蛋白D1和jun N-末端激酶1的表达减少;通过免疫组织化学证实了结构基因产物（E-钙粘蛋白、波形蛋白、α 2-整联蛋白和α-连环蛋白）的这些发现。这些结果与先前注意到的IC和APF处理的正常细胞的增殖率降低相一致，并且表明APF抑制细胞增殖的机制可能涉及刺激细胞增殖的基因的下调沿着抑制细胞生长的基因的上调。
Explanted bladder epithelial cells from patients with interstitial cystitis (IC) have been shown to differ from explanted control cells in several ways, including production of an antiproliferative factor (APF), altered production of certain epithelial growth factors, and rate of proliferation. To better understand the role of the APF in abnormal bladder epithelial cell proliferation in IC, we studied gene expression patterns in normal bladder epithelial cells treated with APF vs. mock APF and compared them to expression patterns in IC vs. normal cells using microarray analysis. Oligo-dT-primed total cellular RNA was labeled with [ P-33] dCTP and hybridized to GeneFilter GF211 microarray membranes ( Research Genetics) containing cDNA for 3,964 human genes. Thirteen genes that function in epithelial cell proliferation or differentiation were consistently differentially expressed in both IC ( compared with control) and APF-treated ( compared with mock APF-treated) normal bladder epithelial cells. The general pattern of gene expression in IC and APF-treated cells suggested a less proliferative phenotype, with increased expression of E-cadherin, phosphoribosylpyrophosphate synthetase-associated protein 39, and SWI/SNF complex 170-kDa subunit, and decreased expression of vimentin, alpha2-integrin, alpha1-catenin, cyclin D1, and jun N-terminal kinase 1; these findings were confirmed for the structural gene products (E-cadherin, vimentin, alpha2-integrin, and alpha-catenin) by immunohistochemistry. These results are compatible with the previously noted decreased proliferation rate of IC and APF-treated normal cells, and indicate that the mechanism whereby APF inhibits cell proliferation may involve both downregulation of genes that stimulate cell proliferation along with upregulation of genes that inhibit cell growth.