Molecular mechanism of proliferation of myofibroblasts in diabetic retinopathy

糖尿病视网膜病变肌成纤维细胞增殖的分子机制

基本信息

  • 批准号:
    15590946
  • 负责人:
  • 金额:
    $ 2.24万
  • 依托单位:
  • 依托单位国家:
    日本
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
  • 财政年份:
    2003
  • 资助国家:
    日本
  • 起止时间:
    2003 至 2004
  • 项目状态:
    已结题

项目摘要

Diabetic retinopathy is one of the most important vascular complications in diabetes. It is well known that angiogenesis plays pivotal roles in the development of diabetic retinopathy, but the precise mechanism is still unclear. We have been studied the involvement of dedifferentiation of smooth muscle cells (Sacs) in atherosclerosis and found that the proliferation of Sacs are triggered by simultaneous stimulation of ERK and p38MAPK cascades. We also noted that there are common pathogenesis in atherosclerosis, lung fibrosis, liver fibrosis, and nephritis. Under these circumstances, smooth muscle-like cells, such as Ito cells, lung myofibroblasts, mesangium cells, remarkably proliferate in the lesions. We named this pathogenesis as "Myofibroblastosis" and hypothesized that diabetic retinopathy is also included in this new entity.Using primary culture system of differentiated Sacs, we found that unsaturated lysophosphatidic acid (LPA) is one of the most potent inducer of phenotypic dedifferentiation, and administration of LPA induced progression of intimal thickening in rat carotid artery balloon-injury model (Circulation 108:1746,2003). We also identified new inducer of phenotypic dedifferentiation in the conditioned medium. This factor is a member of EGF family, Epiregulin (Circulation 108:2524,2003). Epiregulin activated both of ERK and p38-MAPK cascades and promptly exchanged the differentiated phenotype of Sacs into dedifferentiated state. Finally, we identified over-expression of EGF family and proliferation of smooth muscle-like cells in the tissue excised from the patients of diabetic retinopathy. We concluded that there is a common pathogenesis in diabetic retinopathy and atherosclerosis.
糖尿病视网膜病变是糖尿病最重要的血管并发症之一。血管生成在糖尿病视网膜病变的发生发展中起着重要作用,但其确切机制尚不清楚。我们已经研究了动脉粥样硬化中平滑肌细胞(Sacs)的去分化,发现Sacs的增殖是由ERK和p38 MAPK级联反应同时刺激触发的。动脉粥样硬化、肺纤维化、肝纤维化、肾炎等疾病也有共同的发病机制。在这种情况下,平滑肌样细胞如Ito细胞、肺肌成纤维细胞、系膜细胞在病变中显著增殖。我们将这种发病机制命名为"肌纤维母细胞增多症",并假设糖尿病视网膜病变也包括在这个新的实体中。使用分化的Sac的原代培养系统,我们发现不饱和溶血磷脂酸(LPA)是表型去分化的最有效的诱导剂之一,并且在大鼠颈动脉球囊损伤模型中给予LPA诱导内膜增厚的进展(Circulation 108:1746,2003)。我们还确定了新的诱导剂的表型去分化的条件培养基。该因子是EGF家族的成员,Epiregulin(Circulation 108:2524,2003)。epiregulin激活ERK和p38-MAPK级联反应,并迅速将已分化的Sac表型转换为去分化状态。最后,我们确定了EGF家族的过度表达和平滑肌样细胞的增殖从糖尿病视网膜病变患者的组织切除。我们的结论是糖尿病视网膜病变和动脉粥样硬化有一个共同的发病机制。

项目成果

期刊论文数量(24)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Vascular Remodeling Induced by Naturally Occuring Unsaturated Lysophosphatidic Acid In Vivo
体内天然存在的不饱和溶血磷脂酸诱导的血管重塑
  • DOI:
  • 发表时间:
    2003
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Yoshida K;Nishida W;Hayashi K;Ohkawa Y;Ogawa A;Aoki J;Arai H;Sobue K
  • 通讯作者:
    Sobue K
Epiregulin as a major autocrine/paracrine factor released from ERK- and p38MAPK-activated vascular smooth muscle cells
  • DOI:
    10.1161/01.cir.0000096482.02567.8c
  • 发表时间:
    2003-11-18
  • 期刊:
  • 影响因子:
    37.8
  • 作者:
    Takahashi, M;Hayashi, K;Sobue, K
  • 通讯作者:
    Sobue, K
Takahashi M., Hayashi K.et al.: "Epiregulin as a major autocrine/paracrine factor released from ERK- and p38MAPK-activated vascular smooth muscle cells"Circulation. 108(20). 2524-2529 (2003)
Takahashi M.、Hayashi K.等人:“上皮调节蛋白是 ERK 和 p38MAPK 激活的血管平滑肌细胞释放的主要自分泌/旁分泌因子”循环。
  • DOI:
  • 发表时间:
  • 期刊:
  • 影响因子:
    0
  • 作者:
  • 通讯作者:
Vascular Remodeling Induced by Naturally Occurring Unsaturated Lysophosphatidic Acid In Vivo
  • DOI:
    10.1161/01.cir.0000089374.35455.f3
  • 发表时间:
    2003-10
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Kenji Yoshida;W. Nishida;Ken’ichiro Hayashi;Y. Ohkawa;Akira Ogawa;J. Aoki;H. Arai;K. Sobue
  • 通讯作者:
    Kenji Yoshida;W. Nishida;Ken’ichiro Hayashi;Y. Ohkawa;Akira Ogawa;J. Aoki;H. Arai;K. Sobue
糖尿病合併症増加の因子(1960年代網膜症はまれであった)
导致糖尿病并发症增加的因素(视网膜病变在 20 世纪 60 年代很少见)
  • DOI:
  • 发表时间:
    2004
  • 期刊:
  • 影响因子:
    0
  • 作者:
    西田 亙;牧野 英一
  • 通讯作者:
    牧野 英一
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NISHIDA Wataru其他文献

NISHIDA Wataru的其他文献

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{{ truncateString('NISHIDA Wataru', 18)}}的其他基金

Establishment of anti human monoclonal antibody clones using cell-free protein translation system and development of automatic measurement system of human resistin.
利用无细胞蛋白翻译系统建立抗人单克隆抗体克隆并开发人抵抗素自动测定系统。
  • 批准号:
    22590530
  • 财政年份:
    2010
  • 资助金额:
    $ 2.24万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Smooth muscle-specific transcriptional regulation by SRF and homeodomain proteins
SRF 和同源域蛋白的平滑肌特异性转录调节
  • 批准号:
    11838010
  • 财政年份:
    1999
  • 资助金额:
    $ 2.24万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)

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使用社会价值判断知情的分配成本效益分析评估糖尿病视网膜病变筛查的公平性(压迫框架知情的糖尿病视网膜病变筛查公平成本效益分析)
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Roles of histone modifications in a mounse ischemic retinopathy model
组蛋白修饰在 mounse 缺血性视网膜病变模型中的作用
  • 批准号:
    23K09023
  • 财政年份:
    2023
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    $ 2.24万
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    Grant-in-Aid for Scientific Research (C)
Atypical opsins and the OIR model of retinopathy of prematurity
非典型视蛋白与早产儿视网膜病变的 OIR 模型
  • 批准号:
    10675898
  • 财政年份:
    2023
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    $ 2.24万
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Surrogate Augmented Deep Predictive Learning for Retinopathy of Prematurity
早产儿视网膜病变的替代增强深度预测学习
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    10740289
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Subclass analysis of IL-17A and osteopontin-producing T cells involved in the development of diabetic retinopathy
IL-17A 和骨桥蛋白生成 T 细胞参与糖尿病视网膜病变发展的亚类分析
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    23K09036
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    2023
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    Grant-in-Aid for Scientific Research (C)
Novel non-invasive approach for predicting retinopathy of prematurity in premature neonates
预测早产儿视网膜病变的新型非侵入性方法
  • 批准号:
    10665438
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Validation of artificial intelligence (AI) based software as medical device (SaMD) for retinopathy of prematurity (ROP)
验证基于人工智能 (AI) 的软件作为治疗早产儿视网膜病变 (ROP) 的医疗设备 (SaMD)
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    2023
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    $ 2.24万
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OCTA Precursors of Vision-Threatening Complications of Diabetic Retinopathy
OCTA 糖尿病视网膜病变视力威胁并发症的前兆
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    10718643
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The Genetic Architecture of Diabetic Retinopathy
糖尿病视网膜病变的遗传结构
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糖尿病视网膜病变中的脑-肠-视网膜轴
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