Physiological and pathological analysis of BMP-3b in cardiovascular system.

BMP-3b在心血管系统中的生理病理分析。

• 批准号: 18590830
• 负责人: HINO Jun
• 金额: $ 2.41万
• 依托单位: National Cardiovascular Center Research Institute
• 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-18590830/
• 关键词: BMP-3b; BMP; vascular smooth muscle cells; arteriosclerosis; splicing variant; transgenic mice; cardiopoiesis; 分子型; TGF-b

BMP-3b was originally isolated from femur and have antagonistic activity against BMP-2 in osteoblast and developing embryos. Although BMP-3b gene was highly expressed in aorta, its function in cardiovascular system is still unknown. Regarding the BMPs function in that system, it has been now active and being progress since the paper which reported that mutation of BMP receptor caused PPH was published in 2000. To clarify the function of BMP-3b in cardiovascular system, we first examined the effect of that in cultured aortic smooth muscle cells. BMP-3b gene was expressed in both in rat and human cells and level of that was changed by the preparation method(enzyme and explant method) . The biological activity was examined by adenovirus over-expression system. The result showed that BMP-3b had growth inhibitory effect. During cloning of the intrinsic form of BMP-3b in these cells, we isolated new splicing variant that was never known. In this new variant, essential part of BMP-3b activity of the protein was deleted, suggesting that there would be novel activity and molecular form of BMP-3b. Next, we examined the function of BMP-Sb in the heart. In the cultured cells from neonatal rat, BMP-3b gene was expressed both in myocyte and non-myocyte cells. In the developing stage of the heart(embryo d8.5 to d10.5), BMP-3b gene expression was observed through the entire stage and the level increased with stage. In addition, we have just generated TG mice overexpressing BMP-3b especially in heart, BMP-3b expression level was 10 to 100 times higher than wild ones in heart. Now we are breeding and examining these mice. We developed antibody specific for BMP-3b and investigated the molecular form of BMP-3b. We found that the molecular form of secreted BMP-3b was unique that was never reported in BMP family, so we are now checking the molecular form in rat tissues where BMP-3b was highly expressed.

BMP-3b 最初是从股骨中分离出来的，在成骨细胞和发育中的胚胎中具有对抗 BMP-2 的活性。尽管BMP-3b基因在主动脉中高表达，但其在心血管系统中的功能仍不清楚。关于BMPs在该系统中的功能，自2000年报道BMP受体突变导致PPH的论文发表以来，现在一直很活跃并正在取得进展。为了阐明BMP-3b在心血管系统中的功能，我们首先检查了其作用在培养的主动脉平滑肌细胞中。 BMP-3b基因在大鼠和人细胞中均表达，且其水平因制备方法（酶法和外植体法）而改变。采用腺病毒过表达系统检测其生物学活性。结果表明BMP-3b具有生长抑制作用。在这些细胞中克隆 BMP-3b 的内在形式的过程中，我们分离出了未知的新剪接变体。在这个新的变体中，该蛋白的BMP-3b活性的重要部分被删除，这表明BMP-3b将会有新的活性和分子形式。接下来，我们检查了 BMP-Sb 在心脏中的功能。在新生大鼠培养细胞中，BMP-3b基因在肌细胞和非肌细胞中均有表达。在心脏发育阶段（胚胎d8.5至d10.5），整个阶段均观察到BMP-3b基因表达，且水平随阶段增加而增加。此外，我们刚刚培育出BMP-3b过度表达的TG小鼠，尤其是在心脏中，BMP-3b在心脏中的表达水平比野生小鼠高10至100倍。现在我们正在饲养和检查这些小鼠。我们开发了 BMP-3b 特异性抗体并研究了 BMP-3b 的分子形式。我们发现分泌的BMP-3b的分子形式是独特的，在BMP家族中从未报道过，因此我们现在正在检查BMP-3b高表达的大鼠组织中的分子形式。

项目成果

Different cement grand formation by BMP-3b and BMP-3.

BMP-3b和BMP-3形成不同的水泥大地层。

• 发表时间: 2007
• 作者: Nishimatsu S; Hino J; Kangawa K; Matsuo H; Nohno T.
• 通讯作者: Nohno T.

PC6, a BMP-3b-processing enzyme, is involved in axial patterning of the Xenopus embryo.

PC6 是一种 BMP-3b 加工酶，参与非洲爪蟾胚胎的轴向模式形成。

• 发表时间: 2006
• 作者: Nishimatsu S; Hino J; Kangawa K; Matsuo H; Nohno T.
• 通讯作者: Nohno T.

Regulator of G-Protein Signaling Subtype 4 Mediates Antihypertrophic Effect of Locally Secreted Natriuretic Peptides in the Heart

G 蛋白信号亚型 4 的调节剂介导心脏局部分泌的利尿钠肽的抗肥厚作用

• DOI: 10.1161/circulationaha.107.732990
• 发表时间: 2008-05-06
• 期刊: Circulation
• 影响因子: 37.8
• 作者: T. Tokudome;I. Kishimoto;T. Horio;Yuji Arai;D. Schwenke;J. Hino;I. Okano;Y. Kawano;M. Kohno;M. Miyazato;K. Nakao;K. Kangawa
• 通讯作者: K. Kangawa

Regulator of G-protein signaling subtype 4 mediates antihypertrophic effect of locally secreted natriuretic peptides in the heart.

G 蛋白信号亚型 4 的调节剂介导心脏局部分泌的利尿钠肽的抗肥厚作用。

• 发表时间: 2008
• 作者: Tokudome T; Kishimoto I; Horio T; Arai Y; Schwenke DO; Hino J; Okano I; Kawano Y; Kohno M; Miyazato M; Nakao K; Kangawa K.
• 通讯作者: Kangawa K.

BMP-3bとBMP-3によるセメント腺形成メカニズムの相違

BMP-3b和BMP-3形成水泥腺机制的差异

• 发表时间: 2007
• 作者: 西松 伸一郎; 他
• 通讯作者: 他