Role of Wnt signaling in cardiomyocyte differentiation and its implication for the treatment of heart diseases

Wnt信号在心肌细胞分化中的作用及其对心脏病治疗的意义

• 批准号: 21229010
• 负责人: KOMURO Issei
• 金额: $ 135.53万
• 依托单位: The University of Tokyo (2013)Osaka University (2010-2012)Chiba University (2009)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (S)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009-05-11 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21229010/
• 关键词: 循環器・高血圧; 発生・分化; Wntシグナル; iPS細胞; 間葉系幹細胞; 心不全; 心筋細胞; 多能性幹細胞; 心筋細胞分化; Wnt; C1q; ES細胞; IGFBP-4

Patients with heart diseases are increasing in number, and elucidation of the pathophysiology and development of novel therapeutic strategies for heart diseases are mandatory. Wnt signaling pathway plays multiple roles in development and diseases, and recent studies have also implicated Wnt signaling both in heart development during embryogenesis and heart diseases in the adult. In the present study, we have clarified the molecular mechanism how IGFBP4 inhibits Wnt signaling and promotes heart development. We have also identified that activation of Wnt signaling followed by inhibition of Wnt signaling by using small molecules can efficiently induce cardiac differentiation of human iPS cells and mouse mesenchymal stem cells. Finally, we have identified that complement protein C1q is increased in the serum of heart failure model mice and may play detrimental role in the progression of heart failure.

随着心脏病患者数量的不断增加，阐明心脏病的病理生理学和开发新的治疗策略势在必行。Wnt信号通路在发育和疾病中发挥着多种作用，最近的研究也发现Wnt信号通路在胚胎期心脏发育和成人心脏病中都有作用。在本研究中，我们阐明了IGFBP4抑制Wnt信号并促进心脏发育的分子机制。我们还发现，激活Wnt信号，然后用小分子抑制Wnt信号，可以有效地诱导人类iPS细胞和小鼠间充质干细胞的心脏分化。最后，我们发现补体蛋白C1q在心力衰竭模型小鼠血清中升高，可能在心力衰竭的进展中起不利作用。

项目成果

Prognostic impact of left ventricular noncompaction in patients with Duchenne/Becker muscular dystrophy - Prospective multicenter cohort study

• DOI: 10.1016/j.ijcard.2012.12.058
• 发表时间: 2013-10-03
• 期刊: INTERNATIONAL JOURNAL OF CARDIOLOGY
• 影响因子: 3.5
• 作者: Kimura, Koichi;Takenaka, Katsu;Komuro, Issei
• 通讯作者: Komuro, Issei

A novel heart failure mice model of hypertensive heart disease by angiotensin II infusion, nephrectomy, and salt loading

• DOI: 10.1152/ajpheart.00349.2013
• 发表时间: 2013-12-01
• 期刊: AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
• 影响因子: 4.8
• 作者: Tsukamoto, Yasumasa;Mano, Toshiaki;Komuro, Issei
• 通讯作者: Komuro, Issei

スタチンの心不全・心房細動に及ぼす効果

他汀类药物对心力衰竭和心房颤动的影响

• 发表时间: 2009
• 作者: Martinez;G.;et al.;Miho Ohsugi;小室一成
• 通讯作者: 小室一成

A crucial role for adipose tissue p53 in the regulation of insulin resistance

• DOI: 10.1038/nm.2014
• 发表时间: 2009-09-01
• 期刊: NATURE MEDICINE
• 影响因子: 82.9
• 作者: Minamino, Tohru;Orimo, Masayuki;Komuro, Issei
• 通讯作者: Komuro, Issei

診療に活かす心機能評価

心脏功能评估在医疗中的应用

• 发表时间: 2009
• 作者: 塩島一朗;小室一成
• 通讯作者: 小室一成