The functions and regulatory mechanism the expression of the tenascin family during tissue remodeling of myocardium.

腱蛋白家族表达在心肌组织重塑过程中的功能及调控机制。

• 批准号: 08670781
• 负责人: YOSHIDA Kyoko
• 金额: $ 0.96万
• 依托单位: Mie University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08670781/
• 关键词: Tenascin; Extracellular Matrix; Tissue remodeling; knock out; myocardial infarction; embryo; heart; 心筋細胞; 細胞接着; 冠動脈

To clarify the roles and the expression regulation mechanism, we examined the localization of tenascin-C and its producing cells during myocardial tissue remodeling. Tenascin-C,which was not expressed in normal adult heart, was re-expressed by interstitial cells in myocardium of various experimental animal models, human autopsy or biopsy specimen. In case of acute myocardial infarction, tenascin-C appeared during acute phase at only the edge of residual myocardium.Next, we analyzed the spatiotemporal distribution of tenascin-C and tenascin-X during the heart development of mouse embryos. Tenascin-C transiently appeared in (1) epithelializing and differentiating precardiac mesoderm (2) migrating endocardial cells into cardiac jelly, and (3) migrating proepicardial cells from transverse septum.Tenascin-X was reciprocally expressed by epicardial cells migrating into myocardium after the expression of tenascin-X was downregulated. Tenascin-C null mice did not show any distinct phenotype. We have not find any indications that tenascin-X compensated tenascin-C.Furthermore, we examined factors which stimulate cardiac fibroblasts to synthesis tenascin-C in vitro. We have found that TGF-beta1, bFGF,angiotensin II,mechanical stretch, low pH,hypoxia induce the expression of tenascin-C.

为了阐明Tenascin-C的作用和表达调控机制，我们研究了Tenascin-C及其产生细胞在心肌组织重塑过程中的定位。Tenascin-C在正常成人心脏中不表达，但在各种实验动物模型、人体尸检和活检标本的心肌间质细胞中重新表达。在急性心肌梗死时，Tenascin-C仅出现在残留心肌的边缘。接下来，我们分析了Tenascin-C和Tenascin-X在小鼠胚胎心脏发育过程中的时空分布。Tenascin-C暂时存在于(1)心前中胚层的上皮化和分化，(2)心内膜细胞迁移成心脏凝胶，(3)迁移至横隔的心外膜细胞。Tenascin-X的表达下调后，迁移到心肌的心外膜细胞可以相互表达Tenascin-X。Tenascin-C基因缺失的小鼠没有表现出任何明显的表型。我们没有发现任何迹象表明Tenascin-X补偿了Tenascin-C。此外，我们在体外检测了刺激心脏成纤维细胞合成Tenascin-C的因素。我们发现，转化生长因子-β1、碱性成纤维细胞生长因子、血管紧张素II、机械拉伸、低pH、低氧均可诱导Tenascin-C的表达。

项目成果

K.Imanaka-Yoshida,A.Amitani,S.O.Ioshii,S.Koyabu,T.Yamakado,and T.Yoshida.: "Alterations of expression and distribution of the CA2+ storing proteins in endo/sarcoplasmic reticulum during differentiation of rat cardiomyocytes." J.Mol.Cell.Cardiol.28. 553-56

K.Imanaka-Yoshida、A.Amitani、S.O.Ioshii、S.Koyabu、T.Yamakado 和 T.Yoshida.：“大鼠心肌细胞分化过程中内质网/肌浆网中 CA2 存储蛋白的表达和分布的变化。”

H.Tsutsui: "Myocyte contractile dysfunction and alterations in sarcoplasmic reticulum Ca regulatory proteins in pressure overload cardiac hypertrophy" Am.J.Physiol.272. H168-175 (1997)

H.Tsutsui：“压力超负荷心脏肥大中的心肌细胞收缩功能障碍和肌浆网 Ca 调节蛋白的变化”Am.J.Physiol.272。

K.Imanaka-Yoshida, K.A.Knudsen, and K.K.Linask.: "N-cadherin is required for the differentiation and initial myofibrillogenesis of chick cardiomyocytes." Cell Motil.Cytoskel. 39. 52-62 (1998)

K.Imanaka-Yoshida、K.A.Knudsen 和 K.K.Linask.：“N-钙粘蛋白是鸡心肌细胞分化和初始肌原纤维形成所必需的。”

H.Tsuitsui,Y.Ishibashi,K.Imanaka-Yoshida,S.Yamamoto,M.Sugimachi,Y.Urabe,and A.: "Takeshita.Myocyte contractile dysfunction and alterations in sarcoplasmic reticulum Ca regulatory proteins in pressure overload cardiac hypertrophy." Am.J.Physiol. in press.

H.Tsuitsui、Y.Ishibashi、K.Imanaka-Yoshida、S.Yamamoto、M.Sugimachi、Y.Urabe 和 A.：“Takeshita。压力超负荷心脏肥大中肌细胞收缩功能障碍和肌浆网 Ca 调节蛋白的变化。

T.Yamakado, E.Takagi, S.Okubo, K.Imanaka-Yoshida, M.Nakamura, and T.Nakano.: "Effects of aging on left ventricular relaxation in human subjects. Analysis of left ventricular isovolemic pressure decay." Circulation. 95. 917-923 (1997)

T.Yamakado、E.Takagi、S.Okubo、K.Imanaka-Yoshida、M.Nakamura 和 T.Nakano.：“衰老对人类受试者左心室舒张的影响。左心室等容压衰减分析。”