Enhanced urokinase plasminogen activation in chronic pancreatitis suggests a role in its pathogenesis.
Enhanced urokinase plasminogen activation in chronic pancreatitis suggests a role in its pathogenesis.
复制标题
慢性胰腺炎中尿激酶纤溶酶原激活增强表明在其发病机制中发挥作用。
DOI：
10.1016/s0016-5085(97)70186-0
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发表时间：
1997
期刊：
影响因子：
29.4
通讯作者：
Büchler,MW
中科院分区：
文献类型：
--
作者：
Friess,H;Cantero,D;Graber,H;Tang,WH;Guo,X;Kashiwagi,M;Zimmermann,A;Gold,L;Korc,M;Büchler,MW
尿激酶型纤溶酶原激活物（uPA）调节纤溶酶原产生纤溶酶.为探讨纤溶酶原激活物/纤溶酶系统在慢性胰腺炎（CP）中的作用，采用北方印迹法、原位杂交和免疫组织化学方法，检测14例CP患者胰腺切除术后uPA及其受体（uPAR）、纤溶酶原激活物抑制物1（派-1）和转化生长因子β 1（TGF-β 1）的表达。14例CP中uPA（5.2倍）、uPAR（5.9倍）和TGF-β 1（8.8倍）mRNA的表达均高于正常对照组（P < 0.001）。派-1 mRNA表达在所有CP样品中均增加（6.5倍; P < 0.001）。通过原位杂交，中度到强烈的mRNA染色的所有四个因素存在于腺泡细胞，一些导管细胞，和地区与导管化生的CP样品。免疫组化发现类似的染色模式。CP样品中所有这些因子的mRNA和免疫染色强度与较高程度的胰腺损伤有关。CONCLUSIONSuPA及其受体可能有助于通过纤溶酶产生在CP中观察到的溶解性损伤。类似地，增加量的纤溶酶可激活潜伏的TGF-β，从而导致纤维化组织的积聚。（胃肠病学1997年9月;113（3）：904-13）
BACKGROUND & AIMSUrokinase 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).METHODSUsing 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.RESULTSEight 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.CONCLUSIONSuPA 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. (Gastroenterology 1997 Sep;113(3):904-13)