• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文OA文献 >Beta-arrestin2 regulates parathyroid hormone effects on a p38 MAPK and NFkappaB gene expression network in osteoblasts
【2h】

Beta-arrestin2 regulates parathyroid hormone effects on a p38 MAPK and NFkappaB gene expression network in osteoblasts

机译：Beta-arrestin2调节甲状旁腺激素对成骨细胞中p38 MAPK和NFkappaB基因表达网络的影响

代理获取
本网站仅为用户提供外文OA文献查询和代理获取服务，本网站没有原文。下单后我们将采用程序或人工为您竭诚获取高质量的原文，但由于OA文献来源多样且变更频繁，仍可能出现获取不到、文献不完整或与标题不符等情况，如果获取不到我们将提供退款服务。请知悉。
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Interaction of the cytoplasmic adaptor molecule beta-arrestin2 with the activated parathyroid hormone (PTH)/PTHrP receptor inhibits G protein mediated signaling and triggers MAPKs signaling. In turn, the effects of both intermittent (i.) and continuous (c.) PTH on bone are altered in beta-arrestin2-deficient (Arrb2(-/-)) mice. To elucidate the expression profile of bone genes responsive to PTH and targeted for regulation by beta-arrestin2, we performed microarray analysis using total RNA from primary osteoblastic cells isolated from wild-type (WT) and Arrb2(-/-) mice. By comparing gene expression profiles in cells exposed to i.PTH, c.PTH or vehicle (Veh) for 2 weeks, we found that i.PTH specifically up-regulated 215 sequences (including beta-arrestin2) and down-regulated 200 sequences in WT cells, about two-thirds of them being under the control of beta-arrestin2. In addition, beta-arrestin2 appeared necessary to the down-regulation of a genomic cluster coding for small leucin-rich proteins (SLRPs) including osteoglycin, osteomodulin and asporin. Pathway analyses identified a main gene network centered on p38 MAPK and NFkappaB that requires beta-arrestin2 for up- or down-regulation by i.PTH, and a smaller network of PTH-regulated genes centered on TGFB1, that is normally repressed by beta-arrestin2. In contrast the expression of some known PTH gene targets regulated by the cAMP/PKA pathway was not affected by the presence or absence of beta-arrestin2 in osteoblasts. These results indicate that beta-arrestin2 targets prominently p38 MAPK- and NFkappaB-dependent expression in osteoblasts exposed to i.PTH, and delineates new molecular mechanisms to explain the anabolic and catabolic effects of PTH on bone.
机译：细胞质衔接子分子β-arrestin2与活化的甲状旁腺激素（PTH）/ PTHrP受体的相互作用抑制G蛋白介导的信号传导并触发MAPKs信号传导。反过来，在缺乏β-arrestin2的（Arrb2（-/-））小鼠中，间歇性（i。）和连续性（c。）PTH对骨骼的影响都会改变。为了阐明响应PTH并靶向β-arrestin2调控的骨基因的表达谱，我们使用了来自野生型（WT）和Arrb2（-/-）小鼠的原代成骨细胞的总RNA进行了微阵列分析。通过比较暴露于i.PTH，c.PTH或运载体（Veh）2周的细胞中的基因表达谱，我们发现i.PTH特异性上调了215个序列（包括β-arrestin2）和下调了200个序列。 WT细胞，其中约三分之二处于β-arrestin2的控制之下。此外，β-arrestin2似乎是下调编码富含亮氨酸的小蛋白（SLRP）的基因组簇的必要条件，这些蛋白包括骨糖蛋白，骨调节蛋白和天冬氨酸。通路分析确定了一个以p38 MAPK和NFkappaB为中心的主要基因网络，该网络需要β-arrestin2来被i.PTH上调或下调，而一个较小的PTH调控基因网络则以TGFB1为中心，而该基因通常被β-抑制。抑制蛋白2。相反，某些已知的由cAMP / PKA途径调控的PTH基因靶标的表达不受成骨细胞中是否存在β-arrestin2的影响。这些结果表明，β-arrestin2显着靶向暴露于i.PTH的成骨细胞中p38 MAPK和NFkappaB依赖性表达，并描述了新的分子机制来解释PTH对骨骼的合成代谢和分解代谢作用。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
代理获取

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号