Fitzner Brit, Walzel Hermann, Sparmann Gisela, Emmrich Jörg, Liebe Stefan, Jaster Robert
Department of Medicine, Division of Gastroenterology, Medical Faculty, University of Rostock, E.-Heydemann-Str. 6, 18057 Rostock, Germany.
Cell Signal. 2005 Oct;17(10):1240-7. doi: 10.1016/j.cellsig.2004.12.012. Epub 2005 Jan 21.
Pancreatic stellate cells (PSCs) play a key role in the development of pancreatic fibrosis, a pathological feature of chronic pancreatitis and pancreatic cancer. Here, we show that activation of rat PSCs in vitro is associated with increased expression of galectin-1 (gal-1) and that gal-1 modulates PSC function. Expression of the lectin was stimulated by fetal calf serum and platelet-derived growth factor. PSCs exposed to exogenous gal-1 proliferated at a higher rate and synthesised more collagen than controls. Gal-1-dependent collagen synthesis was blocked by lactose but not by cellobiose, suggesting that gal-1 acts on PSCs through targeting beta-galactoside-containing glycoconjugates. Analysis of gal-1 signalling in PSCs revealed an activation of the extracellular signal-regulated kinases 1 and 2 and enhanced DNA binding of AP-1 transcription factors. Together, our data implicate gal-1 in PSC activation and suggest further studies to analyse the role of endogenous lectins in the development of pancreatic fibrosis in vivo.
胰腺星状细胞(PSCs)在胰腺纤维化的发展过程中起着关键作用,胰腺纤维化是慢性胰腺炎和胰腺癌的一种病理特征。在此,我们表明,体外培养的大鼠PSCs的激活与半乳糖凝集素-1(gal-1)表达的增加相关,并且gal-1可调节PSCs的功能。该凝集素的表达受到胎牛血清和血小板衍生生长因子的刺激。与对照组相比,暴露于外源性gal-1的PSCs增殖速率更高,合成的胶原蛋白更多。gal-1依赖性胶原蛋白合成被乳糖阻断,但不被纤维二糖阻断,这表明gal-1通过靶向含β-半乳糖苷的糖缀合物作用于PSCs。对PSCs中gal-1信号传导的分析显示,细胞外信号调节激酶1和2被激活,AP-1转录因子的DNA结合增强。总之,我们的数据表明gal-1参与了PSCs的激活,并建议进一步开展研究以分析内源性凝集素在体内胰腺纤维化发展中的作用。