Functional analysis of stap, a novel gene expressed in hepatic stellate cells and fibrotic liver tissue and its significance in clinicopathophysiology

肝星状细胞和纤维化肝组织中表达的新基因stap的功能分析及其临床病理生理意义

• 批准号: 14570497
• 负责人: KAWADA Norifumi
• 金额: $ 2.18万
• 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: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14570497/
• 关键词: stap; stellate cell; heme protein; globin; liver fibrosis; 肝星細胞; 肝線維化; STAP; グロビン; ヘム蛋白

STAP consists of a new class of hexacoordinate globin superfamily, which was recently discovered by a proteomics approach for the rat hepatic stellate cells. Unlike hemoglobin, myoglobin and neuroglobin, cytoglobin/STAP is. ubiquitously expressed in several organs although its deteiled localization is unclarified. Immunohistochemistry and immunoelectronmicroscopy revealed that cytoglobin/STAP 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/STAP 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/STAP expression was augmented by the stimulation with serum, platelet-derived growth factor-BB and transforming growth factor-beta 1. These results indicate that cytoglobin/STAP is a tissue hemoglobin uniquely localized in splanchnic fibroblastic cell lineage and may play a role in fibrotic organ disorder.

STAP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，细胞红蛋白/STAP是。在几种器官中普遍表达，尽管其详细的定位尚不清楚。免疫组化和免疫电镜结果显示，Cytoglobin/STAP仅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/STAP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/STAP表达增强的刺激与血清，血小板衍生生长因子-BB和转化生长因子-β 1。这些结果表明，细胞珠蛋白/STAP是一种组织血红蛋白，唯一定位于内脏成纤维细胞系，并可能发挥作用，在纤维化器官疾病。

项目成果

Nakatani K, Seki S, Kawada N, Kitada T, Yamada T, Sakaguchi H, Kadoya H, Ikeda K, Kaneda K.: "Expression of SPARC by activated hepatic stellate cells and its correlation with the stages of fibrogenesis in human chronic hepatitis"Virchows Arch. 441(5). 466

Nakatani K、Seki S、Kawada N、Kitada T、Yamada T、Sakaguchi H、Kadoya H、Ikeda K、Kaneda K.：“激活的肝星状细胞表达 SPARC 及其与人类慢性肝炎纤维发生阶段的相关性”

Sawai H, Kawada N, et al.: "Characterization of the heme environmental structure of cytoglobin, a fourth globin in humans."Biochemistry. 42. 5133-5142 (2003)

Sawai H、Kawada N 等人：“细胞球蛋白（人类第四种球蛋白）的血红素环境结构的表征。”生物化学。

Okuyama H, Shimahara Y, Kawada N.: "The hepatic stellate cell in the post-genomic era"Histol Histopathol. 17(2). 487-495 (2002)

Okuyama H、Shimahara Y、Kawada N.：“后基因组时代的肝星状细胞”Histol Histopathol。

Kawada N.: "Molecular mechanism of stellate cell activation and therapeutic strategy for liver fibrosis"Comp Hepatol (No abstract available). 3 Suppl 1. S3 (2004)

Kawada N.：“星状细胞激活的分子机制和肝纤维化的治疗策略”Comp Hepatol（无摘要）。

Inagaki Y, Nemoto T, Kushida M, Sheng Y, Higashi K, Ikeda K, Kawada N, Shirasaki F, Takehara K, Sugiyama K, Fujii M, Yamauchi H, Nakao A, De Crombrugghe B, Watanabe T, Okazaki I.: "Interferon alfa down-regulates collagen gene transcription and suppresses

Inagaki Y、Nemoto T、Kushida M、Sheng Y、Higashi K、Ikeda K、Kawada N、Shirasaki F、Takehara K、Sugiyama K、Fujii M、Yamauchi H、Nakao A、De Crombrugghe B、Watanabe T、Okazaki I.：