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Development of preventive for periodontitis by using avtivin that indices apoptosis and suppresses the production of IL-1

利用可指示细胞凋亡并抑制 IL-1 产生的 avtivin 开发牙周炎预防剂

基本信息

批准号：
09557155
负责人：
NISHIHARA Tatsuji
金额：
$ 5.44万
依托单位：
National Institute of Infectious Diseases
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1998
项目状态：
已结题

项目摘要

Activins transduce their signals through binding to activin type I receptor (ActR-I) and activin type II receptor (ActR-II), both containing a serine/threonine kinase domain. In this study, we have clarified the role of activin type I receptors in activin A signaling for growth inhibition in HS-72 mouse B cell hybridoma cells. Overexpression of ActR-I suppressed activin A-induced cell cycle arrest in the G1 phase caused by inhibiting Rb phosphorylation through inducting p21^<CIP1/WAF1> and subsequent apoptosis. In contrast, HS-72 cells that overexpressed ActR-IB facilitated activin A-induced apoptosis. These findings suggest that the ActR-I/ActR-IB expression ratio could regulate cell cycle arrest in the G1 phase and subsequent apoptosis in HS-72 cells induced by activin A.Recently, Activins were found to relay signals from serine/threonine kinase receptors in membrane to nucleus via intracellular Sma-and Mad-related (Smad) proteins. Inhibitory Smad proteins are known to prevent the interaction between the serine/threonine kinase receptors and pathway-restricted Smad proteins. Smad7 was identified as a TGF-beta-inducible antagonist of TGF-beta signaling. In this study, we found that the mRNA expression of Smad7 was induced by activin A in HS-72 cells. The ectopic expression of mouse Smad7 in HS-72 cells suppressed the activin A-induced cell-cycle arrest in the G1 phase by abolishing the activin A-induced expression of p21^<CIP1/WAF1> and hypophosphorylation of retinoblastoma protein.Furthermore, Smad7 expression suppressed activin A-induced apoptosis in HS-72 cells. Thus, our data indicate that Smad7 is an activin A-inducible antagonist of activin A-induced growth arrest and apoptosis of B lineage cells.

激活素通过与激活素I型受体（ActR-I）和激活素II型受体（ActR-II）结合来调节其信号，所述激活素I型受体和激活素II型受体均含有丝氨酸/苏氨酸激酶结构域。在这项研究中，我们已经阐明了激活素I型受体在激活素A信号转导中的作用，以抑制HS-72小鼠B细胞杂交瘤细胞的生长。ActR-I的过表达通过诱导p21^<CIP 1/WAF 1>和随后的凋亡抑制Rb磷酸化而抑制激活素A诱导的细胞周期停滞在G1期。相反，过表达ActR-IB的HS-72细胞促进激活素A诱导的细胞凋亡。这些结果表明，ActR-I/ActR-IB的表达比例可以调节细胞周期阻滞在G1期和随后的细胞凋亡激活素A诱导的HS-72细胞。最近，激活素被发现中继信号从丝氨酸/苏氨酸激酶受体在膜上通过细胞内的Sma和Mad-related（Smad）蛋白到核。已知抑制性Smad蛋白阻止丝氨酸/苏氨酸激酶受体与通路限制性Smad蛋白之间的相互作用。Smad 7被鉴定为TGF-β诱导的TGF-β信号传导拮抗剂。在本研究中，我们发现激活素A诱导HS-72细胞中Smad 7的mRNA表达。小鼠Smad 7在HS-72细胞中的异位表达通过消除激活素A诱导的p21^<CIP 1/WAF 1>表达和视网膜母细胞瘤蛋白的低磷酸化而抑制激活素A诱导的细胞周期停滞在G1期，并抑制激活素A诱导的HS-72细胞凋亡。因此，我们的数据表明，Smad 7是激活素A诱导的B系细胞生长停滞和凋亡的激活素A诱导的拮抗剂。