INDUCTION OF HGF AFTER LIVER INJURIES AND IDENTIFICATION OF INDUCER FOR HGF

肝损伤后 HGF 的诱导以及 HGF 诱导剂的鉴定

• 批准号: 03680173
• 负责人: MATSUMOTO Kunio
• 金额: $ 1.02万
• 依托单位: KYUSHU UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1991
• 资助国家: 日本
• 起止时间: 1991 至 1992
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-03680173/
• 关键词: HGF; Injurin; Liver Regeneration; Renal Regeneration; TGF-beta; IL-1; TGF-β1; 肝細胞増殖因子; 増殖因子

Hepatocyte growth factor(HGF)induces mitogenesis,motogenesis and morphogenesis of various epithelial cells,including mature hepatocytes and has been considered to act as a hepatotrophic factor for liver regeneration.We have studied induction of HGF following various injuries in the liver and kidney and identified inducers for HGF.Expression of HGF was rapidly and markedly induced following onset of various liver injuries(hepatitis,partial hepatectomy,etc.) or renal injuries(unilateral nephrectomy,ischemia,HgCl_2-administration,etc.)not only in injured organ but also in distant intact organs such as lung and spleen.Thus HGF seems to act as hepatotrophic and renotropic factor for regeneration of liver and kidney through a paracrine and an endorine mechanisms.We next found the presence of an inducer for expression of HGF in serum of rat with organ injury and named the factor "injurin".Injurin was partially purified from the serum of rats and was found to be acid-and heat-stable proteious factor with Mr of 10-30kDa.In addition to injurin,interleukin-1(IL-1)and heparin also increased HGF synthesis in cultured fibroblasts,whereas transforming growth factor-beta1(TGF-beta1)and glucocorticoids suppressed expression of HGF,acting as negative regulators for HGF.Injurin,IL-1,and heparin may be rapidly secreted following hepatic or renal injuries and induce expression of HGF.On the other hand TGF-beta1 may be involved in the termination of organ regeneration through its potential to suppress HGF expression.HGF and its regulators may have important roles not only for organ regeneration,but also for organogenesis and homeostasis of organs.

肝细胞生长因子（Hepatocyte growth factor，HGF）诱导包括成熟肝细胞在内的各种上皮细胞的有丝分裂、运动发生和形态发生，被认为是肝再生的促肝细胞生长因子。我们研究了各种肝和肾损伤后HGF的诱导，并鉴定了HGF的诱导剂。或肾损伤（单侧肾切除、缺血、HgCl_2给药等）。HGF不仅存在于损伤器官中，而且也存在于远距离的完整器官如肺、脾中。因此，HGF似乎通过旁分泌和内分泌机制，对肝、肾的再生起着促肝和促肾的作用。我们在器官损伤的大鼠血清中发现了一种诱导HGF表达的因子，并将其命名为“损伤素”。从大鼠血清中部分纯化出损伤素，发现它是一种对酸和热稳定的蛋白质因子，分子量为10- 30 kDa。除损伤素外，白细胞介素-1（IL-1）和肝素也能促进培养的成纤维细胞合成HGF，而转化生长因子β 1（TGF-β 1）和糖皮质激素抑制HGF的表达，作为HGF的负调节剂。肝、肾损伤后肝细胞可迅速分泌肝素，诱导肝细胞生长因子表达。β 1可能通过抑制HGF表达参与器官再生的终止，HGF及其调节因子不仅在器官再生中起重要作用，而且在器官发生和器官的内环境稳定中也起重要作用。

项目成果

"Identification of a fibroblastーderived epithelial morphogen as hepatocyte growth factor." Cell. 67. 901-908 (1991)

“鉴定成纤维细胞来源的上皮形态发生素作为肝细胞生长因子。” 67. 901-908 (1991)

K.Matsumoto,T.Takehara,H.Inoue,M.Hagiya,S.Shimizu and T.Nakamura: "Deletion of kringle domains or the Nーterminal hairpin structure in hepatocyte growth factor results in marked decrease in related biological activities." Biochem.Biophys.Res.Commun.181. 69

K. Matsumoto、T. Takehara、H. Inoue、M. Hagiya、S. Shimizu 和 T. Nakamura：“肝细胞生长因子中 kringle 结构域或 N 末端发夹结构的删除会导致相关生物活性显着降低。”生物物理学研究通讯181。

木下 大成,松本 邦夫,中村 敏一: "肝細胞増殖因子(HGF)〜精製、アッセイ、応用〜「生物薬科学実験法」" 広川書店, (1992)

Taisei Kinoshita、Kunio Matsumoto、Toshikazu Nakamura：“肝细胞生长因子 (HGF) - 纯化、测定、应用 - 生物制药科学实验方法” 广川书店，(1992)

K.Matsumoto and T.Nakamura(ed.I.D.Goldbergの分担): "Roles of HGF as a pleiotropic factor in organ regeneration.In“Hepatocyte Growth Factor-Scatter Factor and c-Met Receptor"" Birkhauser Verlag, 225-249 (1993)

K.Matsumoto 和 T.Nakamura（ed.I.D.Goldberg）：“HGF 作为多效性因子在器官再生中的作用。In“肝细胞生长因子-分散因子和 c-Met 受体””Birkhauser Verlag，225-249（1993）

木下 大成,松本 邦夫,中村 敏一: ""HGFの多様な生理作用と組織再生"" 「サイトカインと情報伝達」実験医学. 144-153 (1992)

Taisei Kinoshita、Kunio Matsumoto、Toshikazu Nakamura：“‘HGF 和组织再生的多种生理效应’”“细胞因子和信息转导”实验医学 144-153 (1992)。