Friess H, Cantero D, Graber H, Tang W H, Guo X, Kashiwagi M, Zimmermann A, Gold L, Korc M, Büchler M W
Department of Visceral and Transplantation Surgery, University of Bern, Inselspital, Switzerland.
Gastroenterology. 1997 Sep;113(3):904-13. doi: 10.1016/s0016-5085(97)70186-0.
BACKGROUND & AIMS: Urokinase plasminogen activator (uPA) regulates plasmin generation from plasminogen. The aim of this study was to analyze the role of the plasminogen activator/plasmin system in chronic pancreatitis (CP).
Using Northern blot analysis, in situ hybridization, and immunohistochemistry, the expression of uPA, its receptor (uPAR), plasminogen activator inhibitor 1 (PAI-1), and transforming growth factor beta 1 (TGF-beta 1) was studied in 14 patients undergoing pancreatic resection for CP. Normal control pancreatic tissue was obtained through an organ donor program.
Eight of 14 CP samples showed concomitant increased expression (P < 0.001) of uPA (5.2-fold), uPAR (5.9-fold), and TGF-beta 1 (8.8-fold) messenger RNA (mRNA) compared with normal controls. PAI-1 mRNA expression was increased (6.5-fold; P < 0.001) in all CP samples. By in situ hybridization, moderate to strong mRNA staining of all four factors was present in acinar cells, some ductal cells, and areas with ductal metaplasia in CP samples. A similar staining pattern was found by immunohistochemistry. Intense mRNA and immunostaining for all of these factors in CP samples was associated with a higher degree of pancreatic damage.
uPA and its receptor may contribute to the lytic damage observed in CP by plasmin generation. Similarly, increased amounts of plasmin may activate latent TGF-beta, thereby leading to the accumulation of fibrotic tissue.
尿激酶型纤溶酶原激活剂（uPA）可调节纤溶酶原生成纤溶酶。本研究旨在分析纤溶酶原激活剂/纤溶酶系统在慢性胰腺炎（CP）中的作用。
采用Northern印迹分析、原位杂交和免疫组织化学方法，对14例因CP接受胰腺切除术的患者进行uPA及其受体（uPAR）、纤溶酶原激活剂抑制剂1（PAI-1）和转化生长因子β1（TGF-β1）表达的研究。正常对照胰腺组织通过器官捐赠项目获得。
与正常对照相比，14例CP样本中有8例显示uPA（5.2倍）、uPAR（5.9倍）和TGF-β1（8.8倍）信使核糖核酸（mRNA）表达同时增加（P < 0.001）。所有CP样本中PAI-1 mRNA表达均增加（6.5倍；P < 0.001）。通过原位杂交，在CP样本的腺泡细胞、部分导管细胞和导管化生区域中，所有这四种因子均呈现中度至强mRNA染色。免疫组织化学也发现了类似的染色模式。CP样本中所有这些因子的强烈mRNA和免疫染色与更高程度的胰腺损伤相关。
uPA及其受体可能通过纤溶酶生成导致CP中观察到的溶解损伤。同样，纤溶酶量的增加可能激活潜伏的TGF-β，从而导致纤维化组织的积累。
