Secretory Control and Intracellular Signal Transduction of Pancreatic Acinar Myofibroblast in Human

人胰腺腺泡肌成纤维细胞的分泌控制和细胞内信号转导

• 批准号: 13670509
• 负责人: ISHIZUKA Yoshiyuki
• 金额: $ 2.3万
• 依托单位: Shiga University of Medical Science
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13670509/
• 关键词: hPFCs; Matrix metalloproteinase-1; Cytokines; Intracellular signal trancduction; MAPK; PKC; Northern blot; Zymography; Matrix metalloproteienase-1; Nortern blot; ヒト膵腺房由来Myofibroblast; Matrix metalloproteinases; シグナル伝達; protein kinase C; MAP

We confirmed that matrix metalloproteinases(MMPs, MMP-1, 2, 9) were secreted from human pancreatic periacinar fibroblast-like cells(hPFCs) by gelatin gel zymography. A little amount of MMPs secretion were continuously observed in the absent of stimulants and that was remarkably enhanced in the presence of pro-inflammatory cytokines like IL-1β and TNF-α. Enhanced secretion induced by an application of IL-1β and TNF-α were reduced by an application of apigenin, a MAPK inhibitor and PD98059, a MEK inhibitor in a dose dependent manner, but not PKC inhihitor and SB203580, a p38 MAPK inhibitor.It was demonstrated that PKC-independent and MEK dependent signaling pathways induced by pro-inflammatory cytokines were closely concerned with MMP-producing system by a northern blot analysis. The inhibitors of NF-κB(PTDC, TPCK) had no effect on MMP-1 mRNA expression induced by an application of pro-inflammatory cytokines, therefore it was suggested that PDTC and TPCK not blockable transcriptional factors could be worked. Taken together, it resulted that pro-inflammatory cytokines stimulated MMPs production from hPFCs via some regulatory mechanisms involving MEK related signaling path ways.

明胶酶谱检测证实人胰腺腺泡周成纤维细胞(HPFC)分泌基质金属蛋白酶(MMPs，MMPs)。在没有刺激剂的情况下，持续观察到少量MMPs的分泌，而在IL-1、β和肿瘤坏死因子-α等促炎细胞因子的存在下，MMPs的分泌明显增强。丝裂原活化蛋白激酶抑制剂芹菜素和β抑制剂PD98059均能剂量依赖性地抑制IL-1MAPK和肿瘤坏死因子-α诱导的细胞分泌增加，而p38MAPK抑制剂SB203580和p38MAPK抑制剂对其无明显影响。NF-κB的抑制剂(PTDC、TPCK)对促炎细胞因子诱导的MMP1mRNA表达无明显影响，提示PDTC和TPCK不是可阻性转录因子。综上所述，促炎性细胞因子通过一些涉及MEK相关信号通路的调节机制刺激hPFC产生MMPs。

项目成果

馬場忠雄, 五月女隆男, 新谷寛: "ヒト膵腺房周囲筋線維芽細胞のmatrix wetalloproteinase-1(MMP-1)産生におけるシグナル伝達"厚生労働省特定疾患対策事業難治性膵疾患に関する調査研究班平成12年度研究報告書. 228-232 (2001)

马场忠雄、五月高夫、新谷宏：“人胰腺腺泡周围肌成纤维细胞中基质湿蛋白酶-1（MMP-1）生成的信号转导”厚生劳动省特定疾病对策事业、难治性胰腺疾病研究组2000年年度研究报告。228-232（2001）

新谷 寛, 馬場忠雄: "慢性膵炎 わが国の実態,成因と発症機序・進展機序"図説消化器病シリーズ14 膵炎,膵癌 平成13年1月. 84-98 (2001)

Hiroshi Shintani、Tadao Baba：“慢性胰腺炎：日本的实际情况、原因、发病和进展机制”胃肠道疾病系列图解 14 胰腺炎、胰腺癌 2001 年 1 月。84-98 (2001)

新谷寛, 馬場忠雄: "慢性膵炎わが国の実態,成因と発症機序・進展機序"図説消火器病シリーズ14膵炎,膵癌. 84-98 (2001)

Hiroshi Shintani、Tadao Baba：“日本的慢性胰腺炎、其病因、发病机制和进展机制”图解灭火器疾病系列 14 胰腺炎、胰腺癌 84-98 (2001)。

Nakamura F, Shintani Y, Saotome T, et al.: "Effects of Serine Protease Inhibitors on Proliferation and Collagen Synthesis of Human Pancreatic Periacinar Fibroblast-like-Cells"Pancreas. 22. 317-325 (2001)

Nakamura F、Shintani Y、Saotome T 等人：“丝氨酸蛋白酶抑制剂对人胰腺周围成纤维细胞样细胞增殖和胶原蛋白合成的影响”胰腺。

馬場忠雄, 五月女隆男, 新谷 寛: "ヒト膵腺房周囲筋線維芽細のmatrix metalloproteinase-1 (MMP-1)産生におけるシグナル伝達"厚生労働省特定疾患対策事業 難治性膵疾患に関する調査研究班 平成12年度研究報告書 平成13年3月発行. 228-232 (2001)

马场忠雄、五月高夫、新谷宏：“人胰腺腺泡周围肌成纤维细胞中基质金属蛋白酶-1（MMP-1）产生的信号转导”厚生劳动省特定疾病管理项目难治性胰腺疾病研究组2000年年度研究报告2001 年 3 月出版。228-232 (2001)