Molecular mechanism of Onset of Acute Pancreatily in Pancreatic Acinar Cells

胰腺腺泡细胞急性胰腺病发病的分子机制

• 批准号: 14570450
• 负责人: OHNISHI Hirohide
• 金额: $ 2.24万
• 依托单位: Jichi Medical School
• 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-14570450/
• 关键词: Pancreatitis; Syntoxin; vacuolation; Pancreatic cell; 空胞形成; vacuolation; Smad; TGF-β; Activin; 小胞輸送; 膵線組化

Although the precise molecular mechanism of the onset of acute pancreatitisis is still unclear, the intracellular vacuolation formed by the heterotopic fusion of lysozomes and zymogen granules is assumed to be the pathogenic early event in the acute pancreatitis. To elucidate the molecular mechanism of the pathological vacuolation, we conducted this study to investigate the involvement SNARE proteins in the abnormal vacuolation using the model system of intracellular vacuolation formed by cytotoxin VacA (J.Olin.Invest. 107 : 363-370, 2001). We have elucidated that syntaxin 7, a member of SNARE family, is involved in the pathological intracellular vacuolation (J.Biol.Chem. 278 : 25585-25590, 2003). We extended our study to elucidate the molecular mechanism of pancreatic fibrosis, which results from acute pancreatitis, using isolated pancreatic stellate cells. We have shown that acvitin A, a member of TGF-β family, is an autocrine activator of pancreatic stellate cells. We have further revealed that TGF-β family activates pancreatic stellate cells and promotes their growth through distinct Smads-dependent pathways.

虽然急性胰腺炎发病的确切分子机制尚不清楚，但溶酶体和酶原颗粒异位融合形成的细胞内空泡化被认为是急性胰腺炎发病的早期事件。为了阐明病理性空泡形成的分子机制，我们利用细胞毒素VacA形成的细胞内空泡形成模型系统，研究了SNARE蛋白参与异常空泡形成的机制。[j]。我们已经阐明syntaxin 7，一个SNARE家族的成员，参与病理胞内空泡形成（J.Biol.Chem）。[j] .农业科学与技术，2003。我们扩展了我们的研究，以阐明急性胰腺炎引起的胰腺纤维化的分子机制，使用分离的胰腺星状细胞。我们已经证明TGF-β家族成员活化素A是胰腺星状细胞的自分泌激活剂。我们进一步发现TGF-β家族通过不同的smads依赖途径激活胰腺星状细胞并促进其生长。

项目成果

Ohno H., et al.: "Localization of p0071-interacting proteins in epithelial cells"Oncogene. 21. 7042-7049 (2002)

Ohno H.等人：“上皮细胞中 p0071 相互作用蛋白的定位”癌基因。

Hirohide Ohnishi: "Distinct roles of Smad2-, Smad3-, and ERK-dependent pathways in TGF-β_1 regulation of pancreatic stellate cellular functions"J.Biol.Chem.. 279. 8873-8878 (2004)

Hirohide Ohnishi：“Smad2、Smad3 和 ERK 依赖性途径在 TGF-β_1 调节胰腺星状细胞功能中的独特作用”J.Biol.Chem.. 279. 8873-8878 (2004)

Nobuki Ohnishi: "Activin A is an autocrine activator of rat pancreatic stellate cells."Gut. 52. 1487-1493 (2003)

Nobuki Ohnishi：“激活素 A 是大鼠胰腺星状细胞的自分泌激活剂。”肠道。

Hama K.et al.: "Angiotensin II stimulates DNA synthesis of rat pancreatic stellate cells by activating ERK through EGF receptor transactivation."Biochem.Biophys.Res.Commun.. vol.315. 905-911 (2004)

Hama K.等人：“血管紧张素 II 通过 EGF 受体反式激活激活 ERK，刺激大鼠胰腺星状细胞的 DNA 合成。”Biochem.Biophys.Res.Commun. vol.315。

Mashima H, et al.: "A novel mitochondrial Ca^<2+>-dependent solute carrier in the liver identified by mRNA differential display"J.Biol.Chem.. (in press).

Mashima H等人：“通过mRNA差异显示鉴定出肝脏中新型线粒体Ca 2+ 依赖性溶质载体”J.Biol.Chem..（出版中）。