Investigation for the role of collagen-binding integrin receptor in the development of renal fibrosis

胶原结合整合素受体在肾纤维化发展中的作用研究

• 批准号: 14570748
• 负责人: KAGAMI Shoji
• 金额: $ 2.37万
• 依托单位: The University of Tokushima
• 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-14570748/
• 关键词: Integrin; ECM remodeling; ERK-AP1 signaling; Glomerular sclerosis; ILK; ラット抗Thy-1腎炎; MMP; エンドセリン

In order to prevent the progression of renal diseases, we investigated the role of collagen-binding integrin receptor in the development of renal fibrosis. Cell proliferation, migration and collagen contraction assays revealed that both alf3l integrin-mediated ERK/AP-1 and lintegrin-linked kinase (ILK)signalings are important pathways for pathological ECM remodeling seen in progressive glomerulonephritis (GN). Either function-blocking antibody, ERK inhibitor (PD98059) or dominant negative cDNA vector inhibited integrin-mediated signaling on in vitro ECM remodeling seen in progressive GN. Administration of integrin function-blocking anti-α1 integrin antibody into rats with anti-Thy-1 GN showed histological improvement with respect to MC proliferation and abnormal ECM remodeling compared with control anti-Thy-1 GN rats received control antibody. These results indicate that integrin-mediated signaling pathways play a critical role in pathological ECM remodeling in progressive renal fibrosis.

为了预防肾脏疾病的发展，我们研究了胶原结合整合素受体在肾纤维化发展中的作用。细胞增殖、迁移和胶原收缩实验显示，alf3l整合素介导的ERK/AP-1和lintegrin-linked kinase （ILK）信号都是进行性肾小球肾炎（GN）中病理ECM重塑的重要途径。功能阻断抗体、ERK抑制剂（PD98059）或显性负cDNA载体均可抑制进行性GN中整合素介导的体外ECM重塑信号。整合素功能阻断型抗α1整合素抗体对抗thy -1 GN大鼠的MC增殖和异常ECM重塑的组织学影响较给予对照抗体的抗thy -1 GN大鼠明显改善。这些结果表明，整合素介导的信号通路在进行性肾纤维化的病理ECM重塑中起关键作用。

项目成果

Kagami S et al.: "Effects of anti-a 1 integrin subunit antibody on anti-Thy-1 glomerulonephritis."Lab Invest. 82. 1219-1227 (2002)

Kagami S 等人：“抗 a 1 整合素亚基抗体对抗 Thy-1 肾小球肾炎的影响。”Lab Invest。

Kitamura A et al.: "Endothelin-1 is a potent stimulator of α1 β1 integrin-mediated collagen matrix remodeling by rat mesangial cells."

Kitamura A 等人：“Endothelin-1 是大鼠系膜细胞 α1 β1 整合素介导的胶原基质重塑的有效刺激剂。”

Shoji Kagami: "PDGF-BB enhances α1β1 integrin-mediated activation of the ERK/AP-1 pathway involved in collagen matrix remodeling by rat mesangial cells."J Cell Physiol. 198. 470-478 (2004)

Shoji Kagami：“PDGF-BB 增强 α1β1 整合素介导的 ERK/AP-1 途径的激活，参与大鼠系膜细胞的胶原基质重塑。”J Cell Physiol。 198. 470-478 (2004)

Akiko Kitamura: "Endothelin-1 is a potent stimulator of α1β1integrin-medilated collagen matrix remodeling by rat mesangial cells"Biochem Biophys Res Commun. 299. 555-561 (2002)

Akiko Kitamura：“Endothelin-1 是大鼠系膜细胞 α1β1 整合素介导的胶原基质重塑的有效刺激剂”Biochem Biophys Res Commun。 299. 555-561 (2002)

Shuji Kondo: "The role of mast cells in acute tubulo-interstitial nephritis with uveitis."Eur J Pediatr. 162. 496-499 (2003)

Shuji Kondo：“肥大细胞在急性肾小管间质性肾炎伴葡萄膜炎中的作用。”Eur J Pediatr。