Trps1 transcription factor represses phosphate-induced expression of SerpinB2 in osteogenic cells.
Trps1 transcription factor represses phosphate-induced expression of SerpinB2 in osteogenic cells.
复制标题
TRPS1转录因子抑制成骨细胞中磷酸盐诱导的SERPINB2的表达。
DOI：
10.1016/j.bone.2020.115673
复制
发表时间：
2020-12
期刊：
影响因子：
4.1
通讯作者：
Napierala D
中科院分区：
文献类型：
--
作者：
Socorro M;Shinde A;Yamazaki H;Khalid S;Monier D;Beniash E;Napierala D
丝氨酸蛋白酶抑制剂SerpinB 2是细胞应激后上调最多的蛋白质之一。这种多功能丝氨酸蛋白酶抑制剂具有多种多样的活性，包括在细胞存活、增殖、分化、免疫和细胞外基质（ECM）重塑中的作用。对癌细胞的研究表明，SerpinB 2的表达直接受到Trps 1转录因子的抑制，Trps 1转录因子是骨骼和牙齿组织矿化的调节因子。在我们以前的研究中，我们鉴定了SerpinB 2作为在矿化过程开始时被磷酸盐（Pi）高度上调的新基因之一，然而SerpinB 2从未涉及矿化组织的形成或稳态。本研究的目的是确定SerpinB 2是否参与产生矿化ECM的细胞的功能，并确定Pi信号传导和Trps 1之间的相互作用，特别是在产生矿化ECM的细胞中SerpinB 2表达的调节。小鼠骨骼和牙齿组织中SerpinB 2表达模式的分析检测到高SerpinB 2蛋白水平，特别是在产生矿化ECM的细胞中。qRT-PCR和Western印迹分析表明，SerpinB 2的表达被成骨细胞中特异性升高的Pi激活。然而，Pi诱导的SerpinB 2的表达被Trps 1的过表达减弱。在2.3Col1a1-Trps 1转基因小鼠的成骨细胞和成牙本质细胞中也检测到SerpinB 2水平降低。染色质免疫沉淀分析（ChIP）显示，在SerpinB 2基因的调节元件上的Trps 1的占有率响应于Pi的变化。与对照组相比，在产生矿化ECM的细胞中SerpinB 2缺陷的后果的体外功能评估中检测到SerpinB 2缺陷细胞中的矿化受损。总之，SerpinB 2在产生矿化ECM的细胞中的高特异性表达、SerpinB 2缺陷细胞的受损矿化以及两种调节矿化组织形成的分子对SerpinB 2表达的调节表明SerpinB 2参与生理矿化。
Serine protease inhibitor SerpinB2 is one of the most upregulated proteins following cellular stress. This multifunctional serpin has been attributed a number of pleiotropic activities, including roles in cell survival, proliferation, differentiation, immunity and extracellular matrix (ECM) remodeling. Studies of cancer cells demonstrated that expression of SerpinB2 is directly repressed by the Trps1 transcription factor, which is a regulator of skeletal and dental tissues mineralization. In our previous studies, we identified SerpinB2 as one of the novel genes highly upregulated by phosphate (Pi) at the initiation of the mineralization process, however SerpinB2 has never been implicated in formation nor homeostasis of mineralized tissues. The aim of this study was to establish, if SerpinB2 is involved in function of cells producing mineralized ECM and to determine the interplay between Pi signaling and Trps1 in the regulation of SerpinB2 expression specifically in cells producing mineralized ECM. Analyses of the SerpinB2 expression pattern in mouse skeletal and dental tissues detected high SerpinB2 protein levels specifically in cells producing mineralized ECM. qRT-PCR and Western blot analyses demonstrated that SerpinB2 expression is activated by elevated Pi specifically in osteogenic cells. However, the Pi-induced SerpinB2 expression was diminished by overexpression of Trps1. Decreased SerpinB2 levels were also detected in osteoblasts and odontoblasts of 2.3Col1a1-Trps1 transgenic mice. Chromatin immunoprecipitation assay (ChIP) revealed that the occupancy of Trps1 on regulatory elements in the SerpinB2 gene changes in response to Pi. In vitro functional assessment of the consequences of SerpinB2 deficiency in cells producing mineralized ECM detected impaired mineralization in SerpinB2-deficient cells in comparison with controls. In conclusion, high and specific expression of SerpinB2 in cells producing mineralized ECM, the impaired mineralization of SerpinB2-deficient cells and regulation of SerpinB2 expression by two molecules regulating formation of mineralized tissues suggest involvement of SerpinB2 in physiological mineralization.
登录
查看更多内容
影响因子：
5.6
作者：
Camalier, Corinne E.;Yi, Ming;Yu, Li-Rong;Hood, Brian L.;Conrads, Kelly A.;Lee, Young Jae;Lin, Yiming;Garneys, Laura M.;Bouloux, Gary F.;Young, Matthew R.;Veenstra, Timothy D.;Stephens, Robert M.;Colburn, Nancy H.;Conrads, Thomas P.;Beck, George R., Jr.
通讯作者：
Beck, George R., Jr.
影响因子：
6.2
作者：
Julien, Marion;Khoshniat, Solmaz;Guicheux, Jerome
通讯作者：
Guicheux, Jerome
影响因子：
3.8
作者：
Goss, Morgan;Socorro, Mairobys;Napierala, Dobrawa
通讯作者：
Napierala, Dobrawa
DOI：
10.1159/000223693
发表时间：
2009-01-01
期刊：
CALCIUM AND BONE DISORDERS IN CHILDREN AND ADOLESCENTS
影响因子：
--
作者：
Bergwitz, Clemens;Jueppner, Harald
通讯作者：
Jueppner, Harald
影响因子：
41.5
作者：
Farrow, Emily G.;White, Kenneth E.
通讯作者：
White, Kenneth E.