ANALYSES OF THE SIGNAL TRANSDUCTION OF NOVEL ANTI-ARTHRITIC FACTOR, FRP, AND ITS EFFECTS ON IMMUNE SYSTEM

新型抗关节炎因子FRP的信号转导及其对免疫系统的影响分析

• 批准号: 18591105
• 负责人: TANAKA Masao
• 金额: $ 2.51万
• 依托单位: Kanazawa Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18591105/
• 关键词: Rheumatoid arthritis; Follistatin-related protein; Two-hybrid method; Cloning; BIACORE; TGF-beta; Activin

1. Molecular interaction analysis of FRP receptor, A7: Our BIACORE studies disclosed that FRP actually bound to A7 and CD14, and also to activin A, follistatin, TGF-beta1. Their K_D values were calculated as follows: 4.20×10^<-6>M for FRP and A7, 1.72×10^<-4>M for FRP and CD14, 1.43×10^<-6>M for FRP and activin A, 1.88×10^<-4>M for FRP and follistatin, 1.28×10^<-8>M for FRP and TGF-beta1. K_D values for other binding pairs could not be decided. FRP was characterized by having extremely high speed and comparatively low affinity binding activity for partner molecules except for TGF-beta. Activin A and CD14 didn't bind to A7, however, follistatin bound weekly and quite slowly to A7, and they all interfered with FRP binding to A7. Interestingly, TGF-beta1 also bound to A7 with relatively-high affinity. However, bound TGF-beta1 seemed to be substituted by a larger amount of FRP, judging from its characteristic rectangular sensorgram. FRP trivially interfered TGF-beta1 binding to TGF-beta1sRII with a little competition, therefore, it seemed that FRP could hardly impede TGF-beta signaling. Taken together, FRP seems to interact with TGF-beta family proteins, and thereby play an important part in the tissue formation including the immune system.2. Cloning of second messengers in FRP signaling system: All of the resultant two-hybrid clone cells, SA240, SA263, SB224, SC21, SC23 proved to lack prey vectors, probably because their product proteins could be toxic to host cells. This brought us to consider cloning by another two-hybrid system not with yeast but with bacteria, whose species is more distant from the mammals.

1. FRP受体A7的分子相互作用分析：我们的BIACORE研究揭示FRP实际上与A7和CD 14结合，也与激活素A、卵泡抑素、TGF-β 1结合。FRP和A7的K_D值为4.20×10^<-6>M，FRP和CD 14的K_D值为1.72×10^<-4>M，<-6>FRP和激活素A的K_D值为1.43×10^M<-4>，FRP和卵泡抑素的K_D值为1.88×10 ^ M，<-8>FRP和TGF-β 1的K_D值为1.28×10^ M。其他结合对的K_D值无法确定。FRP的特征在于对除TGF-β以外的配偶体分子具有极高的速度和相对低的亲和力结合活性。激活素A和CD 14不与A7结合，然而，卵泡抑素每周与A7结合并且非常缓慢，并且它们都干扰FRP与A7的结合。有趣的是，TGF-β 1也以相对较高的亲和力与A7结合。然而，结合的TGF-β 1似乎被大量的FRP取代，从其特征性的矩形传感图判断。FRP对TGF-β 1与TGF-β 1 sRII结合的干扰作用很小，几乎没有竞争，因此，FRP似乎几乎不能阻碍TGF-β信号传导。综上所述，FRP似乎与TGF-β家族蛋白相互作用，从而在包括免疫系统在内的组织形成中发挥重要作用. FRP信号系统第二信使的克隆：所有的双杂交克隆细胞，SA 240，SA 263，SB 224，SC 21，SC 23都被证明缺乏猎物载体，可能是因为它们的产物蛋白可能对宿主细胞有毒性。这使我们考虑用另一种双杂交系统进行克隆，这种系统不是用酵母，而是用细菌，细菌的物种与哺乳动物更远。

项目成果

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• 发表时间: 2008
• 作者: Yoshifuji;H.;Fujii;T.;Kobayashi;S.;Imura;Y.;Fujita;Y.;Kawabata;D.;Usui;T.;Tanaka.M;Nagai;S.;Umehara H.;Mimori;T.;真柄 鮎子;真柄 鮎子;Magara A.;田中 真生;Tanaka M.;Magara A.;田中 真生
• 通讯作者: 田中 真生

Successful treatment of primary Sjogren's syndrome with chronic natural killer lymphocytosis by higy-dose prednisolone and indomethacin farnesil.

大剂量泼尼松龙和吲哚美辛法尼西成功治疗伴有慢性自然杀伤淋巴细胞增多的原发性干燥综合征。

• 发表时间: 2007
• 期刊: Intern. Med. 46・5
• 作者: Fujita Y.;Fujii T.;Takeda N.;Tanaka M.;Mimori T.
• 通讯作者: Mimori T.

Severe subcutaneous generalized edema in a patient with dermatomyositis.

• DOI: 10.1007/s10165-006-0560-9
• 发表时间: 2007-01-01
• 期刊: Modern rheumatology
• 影响因子: 2.2
• 作者: Ito, Yoshinaga;Kawabata, Daisuke;Mimori, Tsuneyo
• 通讯作者: Mimori, Tsuneyo

Analysis of clinical significance of anti-cyclic citrullinated peptide antibody(anti-CCP antibody)in rheumatoid arthritis(RA)

抗环瓜氨酸肽抗体（抗CCP抗体）在类风湿性关节炎（RA）中的临床意义分析

• 发表时间: 2007
• 期刊: Nihon Rinsho Meneki Gakkai Kaishi 30
• 作者: Okuzawa C;et. al.;Fukushima T.;Fujita Y.;Fukushima T.;Fujita Y.;Fukushima T.;Fujita Y.;Dong L.;Umehara H.;Shimoyama K.;Kawanami T.;Dong L.;Umehara H.;Shimoyama K.;Kawanami T.;Dong L.;Shimoyama K.
• 通讯作者: Shimoyama K.

抗CD20抗体(リツキシマブ)療法が有効であったバセドウ病合併SLE難治性血小板減少症の一例

SLE难治性血小板减少症并发格雷夫斯病抗CD20抗体（利妥昔单抗）治疗有效一例

• 发表时间: 2007
• 作者: Yoshifuji;H.;Fujii;T.;Kobayashi;S.;Imura;Y.;Fujita;Y.;Kawabata;D.;Usui;T.;Tanaka.M;Nagai;S.;Umehara H.;Mimori;T.;真柄 鮎子
• 通讯作者: 真柄 鮎子