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Functional analysis of cytoglobin that is expressed and induced in liver cirrhosis

肝硬化中表达和诱导的细胞珠蛋白的功能分析

基本信息

批准号：
16590618
负责人：
KAWADA Norifumi
金额：
$ 2.24万
依托单位：
Osaka City University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2005
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16590618/
关键词：
stellate cell liver fibrosis globin heme oxygen myofibroblast vitamin A 抗ペプチド

项目摘要

Cytoglobin consists of a new class of hexacoordinate globin superfamily, which was recently discovered by a proteomics approach for the rat hepatic stellate cell, an unique fibroblastic cell in the liver. Unlike hemoglobin, myoglobin and neuroglobin, cytoglobin is ubiquitously expressed in several organs including the liver, pancreas, kidney, spleen, intestine and lung, although its detailed localization is unclarified. Immunohistochemistry and immunoelectronmicroscopy revealed that cytoglobin is uniquely localized in fibroblast-like cells in splanchnic organs, namely vitamin A-storing cell lineage, but neither in epithelial cells, endothelial cells, muscle cells, blood cells, macrophages, nor dermal fibroblasts. Expression of cytoglobin was upregulated in fibrotic lesions of pancreas and kidney in which activated fibroblast-like cells or myofibroblasts increased in number. In cultured hepatic stellate cells, cytoglobin expression was augmented by the stimulation with serum, platelet-derived growth factor-BB and transforming growth factor-beta 1. These results indicate that cytoglobin is a tissue hemoglobin uniquely localized in splanchnic fibroblastic cell lineage and may play a role in fibrotic organ disorder. Additional experiments obtained by purified and crystallized cytoglobin revealed that this protein bind oxygen, nitric oxide and carbon monoxide in a manner similar to myoglobin. Thus, cytoglobin is a novel globin that play a role in oxygen transport in visceral myofibroblasts and in contrast myoglobin seems to be a muscle cell-specific oxygen carrier.

细胞红蛋白是近年来通过蛋白质组学方法在大鼠肝星状细胞中发现的一类新的六配位珠蛋白超家族。与血红蛋白、肌红蛋白和神经红蛋白不同，细胞珠蛋白在肝脏、胰腺、肾脏、脾脏、肠和肺等多个器官中普遍表达，尽管其详细定位尚不清楚。免疫组化和免疫电镜结果显示，胞珠蛋白只定位于内脏器官的成纤维样细胞，即维生素A储存细胞系，而不定位于上皮细胞、内皮细胞、肌细胞、血细胞、巨噬细胞和真皮成纤维细胞。在胰腺和肾脏纤维化病变中，细胞珠蛋白的表达上调，其中活化的成纤维细胞样细胞或肌成纤维细胞的数量增加。在培养的肝星状细胞中，细胞珠蛋白的表达增加了血清，血小板衍生生长因子-BB和转化生长因子-β 1的刺激。这些结果表明，细胞红蛋白是一种独特的定位于内脏成纤维细胞系的组织血红蛋白，并可能在器官纤维化疾病中发挥作用。通过纯化和结晶的细胞珠蛋白获得的其他实验表明，这种蛋白质以类似于肌红蛋白的方式结合氧、一氧化氮和一氧化碳。因此，细胞红蛋白是一种新的珠蛋白，在内脏肌成纤维细胞的氧转运中发挥作用，而肌红蛋白似乎是肌细胞特异性的氧载体。

项目成果

期刊论文数量（36）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Cell Type-Specific Intervention of Transforming Growth Factor beta/Smad Signaling Suppresses Collagen Gene Expression and Hepatic Fibrosis in Mice.

转化生长因子β/Smad 信号传导的细胞类型特异性干预可抑制小鼠胶原基因表达和肝纤维化。

DOI：
发表时间：
2005
期刊：
Gastroenterology 129
影响因子：
0
作者：
Inagaki Y;Kushida M;Higashi K;Itoh J;Higashiyama R;Hong YY;Kawada N;Namikawa K;Kiyama H;Bou-Gharios G;Watanabe T;Okazaki I;Ikeda K
通讯作者：
Ikeda K

Cytoglobin/STAP, its unique localization in splanchnic fibroblast-like cells and function in organ fibrogenesis

DOI：
10.1038/labinvest.3700013
发表时间：
2004-01-01
期刊：
LABORATORY INVESTIGATION
影响因子：
5
作者：
Nakatani, K;Okuyama, H;Yoshizato, K
通讯作者：
Yoshizato, K

Structural Characterization of the Proximal and Distal Histidine Environment of Cytoglobin and Neuroglobin

细胞珠蛋白和神经珠蛋白的近端和远端组氨酸环境的结构表征

DOI：
发表时间：
2005
期刊：
Biochemistry 44
影响因子：
0
作者：
T. Nakazato;T. Odagiri;K. Yachi;L. Ishikawa;H. Fukuzawa;H. Miyagi;M. Kitajima;and N. Kouchi;H. Yamazaki;Hitomi Sawaiら
通讯作者：
Hitomi Sawaiら

Analysis of proteins dominantly expressed in hepatic stellate cells of activated phenotype.

活化表型肝星状细胞中主要表达的蛋白质分析。